Mesenteric adenitis means swollen (inflamed) lymph glands in the tummy (abdomen), which causes tummy pain. It is sometimes called mesenteric lymphadenitis. The mesentery is the part of the tummy where the glands are located. Adenitis means inflamed lymph glands.
What is the cause?
Mesenteric adenitis seems to be caused by swollen lymph glands (also called lymph nodes) in the tummy (abdomen). The affected lymph glands are next to the gut (intestine). The swelling of the lymph glands is caused by an infection, usually a viral infection.
Read more about the causes of mesenteric adenitis.
How common is it?
Mesenteric adenitis is a fairly common cause of tummy (abdominal) pain in children aged under 16 years. It is much less common in adults.
What are the symptoms?
Mesenteric adenitis is usually a mild condition which causes temporary pain in the tummy, usually in children. The symptoms of mesenteric adenitis often start following a sore throat or symptoms of a cold. The main symptoms of mesenteric adenitis are:
- A sore throat or symptoms of a cold before the tummy pain started.
- Pain in the tummy. The pain is usually in the middle of your tummy (near your belly button). The pain may be in the lower right-hand side of the tummy (called the right iliac fossa).
- High temperature (fever) and feeling generally unwell.
- Feeling sick (nausea) and/or diarrhoea.
How is it diagnosed?
Mesenteric adenitis is usually diagnosed from your symptoms and an examination of your tummy (abdomen). The only problem is when other more serious conditions can't be ruled out. Tests such as blood tests, a urine test for infection, or scans (ultrasound or CT scan) may be needed to rule out other possible causes of abdominal pain. See also the leaflets called Appendicitis and Abdominal Pain.
Find out more about the diagnosis of mesenteric adenitis.
What is the treatment?
Usually, no treatment is needed for mesenteric adenitis other than painkillers (if needed). If infection with a germ (a bacterial infection) is suspected, you may be given antibiotic medication, but this is uncommon.
Your doctor will advise about the symptoms to look out for which suggest that you should be seen urgently for review. For example, increasing pain or becoming more unwell mean you should seek further advice straightaway.
When might an operation be needed?
In some cases, problems such as appendicitis or ectopic pregnancy cannot be totally ruled out, even after tests. If so, you may need an operation to look inside your tummy to check for any suspected problem. Sometimes this can be done as keyhole surgery (laparoscopy), where a thin fibre-optic telescope is used to look inside the tummy.
If you have an operation or laparoscopy then the inflamed glands may actually be seen. However, the purpose of the operation is not to look for swollen glands, but to make sure other important problems, like appendicitis, are not missed.
What is the outlook?
The symptoms usually improve within a few days, and will almost always clear up completely within about two weeks. Rarely, if infection with a germ (bacterium) is the cause, the condition can become serious if left untreated.
Further reading and references
Kim JS; Acute Abdominal Pain in Children. Pediatr Gastroenterol Hepatol Nutr. 2013 Dec16(4):219-224. Epub 2013 Dec 31.
Humes DJ, Simpson J; Acute appendicitis. BMJ. 2006 Sep 9333(7567):530-4.
Groselj-Grenc M, Repse S, Vidmar D, et al; Clinical and laboratory methods in diagnosis of acute appendicitis in children. Croat Med J. 2007 Jun48(3):353-61.
Hi all,Im freaking out Right now!I have raynauds phonomenom Primary for now as i havent had tests to see if i have Ań underlying cause which i think i do and possibly auto immune related anyway for...MidnightMystery
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Biogenic amines modulate key behaviors in both vertebrates and invertebrates. In Caenorhabditis elegans, tyramine (TA) and octopamine (OA) inhibit aversive responses to 100%, but not dilute (30%) octanol. TA and OA also abolish food- and serotonin-dependent increases in responses to dilute octanol in wild-type but not tyra-3(ok325) and f14d12.6(ok371) null animals, respectively, suggesting that TA and OA modulated responses to dilute octanol are mediated by separate, previously uncharacterized, G-protein-coupled receptors. TA and OA are high-affinity ligands for TYRA-3 and F14D12.6, respectively, based on their pharmacological characterization after heterologous expression. f14d12.6::gfp is expressed in the ASHs, the neurons responsible for sensitivity to dilute octanol, and the sra-6-dependent expression of F14D12.6 in the ASHs is sufficient to rescue OA sensitivity in f14d12.6(ok371) null animals. In contrast, tyra-3::gfp appears not to be expressed in the ASHs, but instead in other neurons, including the dopaminergic CEP/ADEs. However, although dopamine (DA) also inhibits 5-HT-dependent responses to dilute octanol, TA still inhibits in dop-2; dop-1; dop-3 animals that do not respond to DA and cat-2(tm346) and Pdat-1::ICE animals that lack significant dopaminergic signaling, suggesting that DA is not an intermediate in TA inhibition. Finally, responses to TA and OA selectively desensitize after preexposure to the amines. Our data suggest that although tyraminergic and octopaminergic signaling yield identical phenotypes in these olfactory assays, they act independently through distinct receptors to modulate the ASH-mediated locomotory circuit and that C. elegans is a useful model to study the aminergic modulation of sensory-mediated locomotory behaviors.


Epidemiologic evidence supports the positive association of cardiopulmonary morbidity and mortality, and lung cancer risk with exposure to airborne particulate matter (PM). Oxidative stress and inflammation have been proposed to be the major causal factors involved in mediating PM effects on both cardiovascular and pulmonary health outcomes. However, the mechanism whereby PM causes the health effects is not fully elucidated. To evaluate and investigate human exposure to PM, it is essential to have a specific, sensitive and robust characterization of individual exposure to PM. Biomarkers may mark important intermediate steps leading to overt health effects after PM exposure. Thus biomarkers are promising indicators, which could serve as representative measures of the exposure to PM for assessing the health impacts and understanding the mechanism. Indeed, a number of biomarkers are already in use in the field of epidemiological studies and toxicological research. However, we are facing now the challenges to select robust, specific and sensitive biomarkers, which can be employed in large-scale of population to assess the health risk and to monitor the effectiveness of interventions. In this review, we describe a range of biomarkers that are associated with air pollution exposure, particularly markers of oxidative stress, inflammatory factors, and microRNAs, as well as markers of pollutants metabolites. Understanding the nature of the association of these biomarkers with PM exposure may shed some light on the process of selecting biomarkers for large-scale population studies, developing novel preventative and therapeutic strategies.


According to some overly hyped biology professors and students, eugenics is considered to be beneficial and possible. However, it will never be beneficial or possible because it can never work. The reason eugenics may be considered as a possibility is due to the technological advances in genetic engineering. Some people are under the illusion that genetic engineering can finally validate eugenics.
It cannot do this and never will.
Validating eugenics is not only wrong on a moral level but a scientific one. It is difficult to settle an agreement on the morality of eugenics because people may have different moral values, but eugenics cannot be scientifically validated and therefore should never be considered beneficial or valid ever again.
Eugenics is like a weed that keeps popping out of a garden, destroying nutrients for the pretty flowers and vegetables and taking up space when it is completely unnecessary and does not belong in the garden. We need to stop attempting to validate a weed in a garden when the weed does not belong there. Instead of allowing the weed to keep popping up after destroying its leaves, we need to pull it out by the roots. We can scientifically do this with eugenics.
It began with Francis Galton, a knighted polymath-psychologist-inventor-meteorologist-geographer and creator of the concept of correlation. He attempted to ascertain individual differences in psychology and tried to validate eugenics. He believed that only "intelligent" people should reproduce to create a better human race. He tried to follow Mendel's genetic principles to see if this was possible. He believed that there were "defective" families. Guess what, he was wrong.
The reason for this can be understood by Alfred Adler, the founder of the idea of the superiority and inferiority complex. According to Adler, people have a sense of inferiority and try to gain superiority over their environment. This sometimes is applied to feeling superiority over other people. People tried to validate feeling superior to other people via eugenics. These erroneous ideals were manifested in Hitler during World War II. Hitler believed that only the most "purest" blondes and blue-eyed people should procreate because they exhibited Aryan features.
Fortunately, Hitler was proven wrong. There is no intellectual difference in people based upon their skin tone, eye color, hair color, and religion. Although eye color, hair color, and skin tone are more heritable, intelligence is not.
So why are people trying to validate eugenics after Hitler was proven wrong? The answer is genetic engineering.
There are people who believe that they can "design" the perfect child, and these people are also wrong. People need to stop trying to validate eugenics when it is not scientifically possible.
The reason why eugenics will never work is because of the nature vs. nurture controversy. Although we have genomes that give us the material for how we grow and develop, these genes are activated by our environment throughout our lives. Genes are like light switches. If a fetus is given the right nutrients while in the womb, then all the right switches will be turned on and off at the right times. However, genes are also dependent upon how the person interacts with their environment for the rest of their life.
People are under the impression that they can force a child to have all the "right" genes and be a perfect child. However, those genes will not be activated correctly unless that child is under "perfect" environmental conditions.
For argument's sake, let's say that someone could provide the "perfect" environmental conditions for the "perfect" child to grow up. Eugenics still will not work because we don't have one single gene for every trait, talent, or temperament.
According to 23andme.com, there is no gene that gives someone perfect quarterback skills in football. There is no gene that makes someone a perfect dancer, singer, scientist, or doctor. There are no genes that account for kindness, integrity, being goal-oriented, discipline, charisma, or beauty. There may be a gene for dark hair, but not an exact shade. There may be a gene for athletic muscles, but not the entire build of a person's body. We cannot determine the full body shape of genetics.
There is 1 gene associated with episodic memory, 1 gene that is associated with dyslexia, and 1 gene for learning from errors. These 3 genes are the closest to measuring genetic intelligence, but not even these genes can determine full intellectual potential. They can increase the power of episodic memory, severe dyslexia, and learning from errors. Although these traits are associated with intelligence, they cannot fully determine intelligence when they are isolated.
The human genome is too convoluted for eugenics because certain traits are produced from the complex interactions of multiple genes that we do not understand. Even if we could understand them, they would only be activated by the right environmental cues. To make the "perfect" person would be to genetically engineer them and control every single environmental factor in that person's life. It's not possible. The human genome is like clay that is sculpted by the environment to each and every one of us. The environment has a little more power and influence.
Morally, eugenics is also wrong. Eugenics tries to validate superiority complexes of people who are actually on equal ground with everyone else. We are all human. We all convert oxygen into carbon dioxide, we all drink water, and we all matter because we are made of matter and how we feel matters.
Stop trying to validate eugenics because it will always be scientifically and morally wrong.


COP15 on Biodiversity ended this Monday in Montreal. Here is a non-exhaustive press review of the articles published on the subject in the international press.
Biodiversité: Plus de la moitié du PIB mondial dépend de la nature - Saving biodiversity will not happen without them. Major cause of the problem, by their destruction of the ecosystems, the companies are also essential to reverse the tendency because the public money will not be enough. They have in their hands the greening of the economy. (Trends)
Biodiversité : la COP15 s’achève sur un accord surprise - The Chinese presidency of the conference took the negotiators in Montreal by surprise, resulting in a relatively ambitious agreement in the middle of the night. (Le Point)
Cop15: historic deal struck to halt biodiversity loss by 2030 - Agreement on ’30 by 30’ target forced through by Chinese president, ignoring objections from African states. (The Guardian)
La biodiversité, à la fois victime et outil de lutte contre le réchauffement climatique - After the COP27 on climate change, representatives from around the world met in Montreal for the COP15 on Biodiversity, with a new challenge: to approve a roadmap to safeguard nature by 2030. This is a crucial issue, say scientists, especially for the major role that biodiversity plays in the fight against climate change, even though it is one of the first victims. (France24)
FSC at COP 15: Highlighting Forest Stewardship as a Biodiversity Solution - FSC International participated in the second phase of the 15th Conference of the Parties (COP 15) of the UN Convention on Biological Diversity. (FSC)
COP15 : au-delà des promesses, le combat n’est pas gagné sur la biodiversité - More than 190 countries, gathered on Monday at the COP15 in Montreal, have reached a historic agreement to try to stop the destruction of biodiversity. But without a binding mechanism, many of the commitments made are likely to remain unfulfilled.
Some LinkedIn posts about the COP15
Comité français de l’UICN : On December 12 and 13, Florence Clap, Biodiversity Policy Program Officer, participated in the business forum of the COP15 Biodiversity in Montreal.
Wildlife Conservation Society : WCS's Joe Walston spoke yesterday at the UN Biodiversity Conference to remind governments why we are here: CoP15 could be the catalyst for a renaissance for nature.
UN Biodiversity : Nations adopt four goals, 23 targets for 2030 in landmark UN Biodiversity Agreement.
Actu-Environnement : The issue of the exploitation of genetic resources is postponed to COP16
Global Environment Facility : During the CBD COP 15 on Wednesday, 14 December, Carlos Manuel Rodriguez, CEO and Chair, Global Environment Facility (GEF), facilitated a discussion with countries and institutions involved in the conservation of primary forests and their multiple ecosystem services.


B7-H3 is a new member of the B7 family. The receptor for B7-H3 has not been identified, but it seems to be expressed on activated T cells. Initial studies have shown that B7-H3 provides a stimulatory signal to T cells. However, recent studies suggest a negative regulatory role for B7-H3 in T cell responses. Thus, the immunological function of B7-H3 is controversial and unclear. In this study, we investigated the effects of neutralizing anti-B7-H3 mAb in a mouse model of allergic asthma to determine whether B7-H3 contributes to the development of pathogenic Th2 cells and pulmonary inflammation. Administration of anti-B7-H3 mAb significantly reduced airway hyperreactivity with a concomitant decrease in eosinophils in the lung as compared with control IgG-treated mice. Treatment with anti-B7-H3 mAb also resulted in decreased production of Th2 cytokines (IL-4, IL-5, and IL-13) in the draining lymph node cells. Although blockade of B7-H3 during the induction phase abrogated the development of asthmatic responses, B7-H3 blockade during the effector phase did not inhibit asthmatic responses. These results indicated an important role for B7-H3 in the development of pathogenic Th2 cells during the induction phase in a murine model of asthma.
Allergic asthma is characterized by chronic airway inflammation with massive infiltration of eosinophils, increased mucus production in the bronchioles, and airway hyperreactivity (AHR)4 to a variety of specific and nonspecific stimuli. Although a variety of cell types is involved in allergic inflammation, there is substantial evidence that infiltration of Th2 cells is common in the lungs of allergic asthmatic subjects, as are increased levels of Th2 cytokines, including IL-4, IL-5, IL-10, and IL-13, particularly in the late phase (1, 2). The level of Th2 cytokines appears to correlate with severity of disease. These cytokines are responsible for the recruitment and activation of other cell types, including eosinophils, which have been associated with lung injury. They also mediate the production of mucus by the airway epithelium, contributing to the airway obstruction that is a major component of the pathology of asthma (3, 4, 5). Although the critical roles of these Th2 cytokines in the pathogenesis of allergic asthma have been established, the mechanisms for the overproduction of Th2 cytokines in asthmatic responses have not been fully understood.
Optimal activation of Ag-specific T cells requires engagement of the TCR with Ag/MHC and a costimulatory signal provided by APCs (6, 7). It is well known that CD28-B7 (CD80 and CD86) interaction plays a major role in providing a costimulatory signal for T cells (8, 9). Blocking mAb to CD86 inhibits the development of specific IgE, pulmonary eosinophilia, and AHR in mice (10). CTLA-4 is a second receptor for CD80 and CD86, and CTLA4-Ig, a soluble fusion protein, has also been effective in blocking AHR (11, 12). Blockade of these costimulatory pathways markedly reduced allergen-induced asthma in mice, suggesting a promising approach for the treatment of allergic disease in humans.
B7-H3 is a recently identified member of the B7 family (13, 14). Human B7-H3 protein is not expressed constitutively on monocytes, B cells, T cells, or NK cells, but it can be induced on these cell types by some stimulation (13, 15). Mouse B7-H3 mRNA expression is stimulated in dendritic cells (DCs) by IFN-γ, but suppressed by IL-4 (16). LPS stimulates B7-H3 protein expression on mouse DCs, B cells, and macrophages (16). The receptor for B7-H3 has not yet been identified, but it is thought to be expressed by activated T cells and is apparently distinct from other known T cell costimulatory receptors (13, 14). Some studies support roles for B7-H3 as a stimulator or an inhibitor of T cell responses. Initial studies showed that in conjunction with anti-CD3, B7-H3-Ig fusion protein costimulated human CD4+ and CD8+ T cell proliferation and IFN-γ production (13). A subsequent study also showed a costimulatory effect of B7-H3 on tumor immunity in a mouse model (17). However, recent studies have indicated that B7-H3 has an inhibitory function. Proliferation and cytokine production of purified human CD4+ T cells in response to anti-CD3 and anti-CD28 were inhibited by addition of B7-H3-transfected cells (18). Immobilized mouse B7-H3 inhibited mouse CD4+ and CD8+ T cell proliferation and IL-2 and IFN-γ production induced by anti-CD3 (16). Studies with B7-H3-deficient mice also support both stimulatory and inhibitory functions of B7-H3. B7-H3 has been proposed to promote T cell-mediated immune responses, based on the reduced rates of acute and chronic cardiac allograft rejection in B7-H3-deficient mice as compared with wild-type recipients (19). In contrast, under Th1-polarizing condition, B7-H3-deficient mice developed more severe airway inflammation than control wild-type mice (16). Thus, the immunological function of B7-H3 is controversial and still unclear. This study therefore examined the contribution of B7-H3 to the development of allergic asthma by administering a newly generated anti-B7-H3 mAb to a mouse model of asthma, particularly focusing on the role in induction and effector phases. Our present results suggest an important role for B7-H3 in the development of pathogenic Th2 cells during the induction phase, but not in the recruitment and/or activation of Th2 cells in the lung during the effector phase.
Materials and Methods
Animals and cells
Female BALB/c mice were purchased from CLEA Japan. All mice were 6–8 wk old at the start of experiments and kept under specific pathogen-free conditions during the experiments. All animal experiments were approved by Juntendo University Animal Experimental Ethics Committee and complied with National Institutes of Health guidelines for animal care. Six-week-old female Sprague Dawley rats were purchased from Charles River Laboratories. Mice transgenic for the OVA323–339-specific and I-Ad-restricted DO11.10 TCR-αβ on a Rag-2−/− BALB/c background were supplied by S. Koyasu (Keio University School of Medicine, Tokyo, Japan) (20). Stable L5178Y (murine T lymphoma) and P815 (murine mastcytoma) cells expressing B7-1, B7-2, B7-H1 (PD-L1), B7-DC (PD-L2), or B7RP-1 (B7-H2) were established previously (21, 22, 23). A cDNA fragment encoding the entire open reading frame of mouse B7-H3 was prepared by RT-PCR. The PCR product was cloned into pMKITneo vector and transfected into L5178Y and P815 by electroporation. Muirne B7-H4-transfected P815 cells were provided by M. Azuma (Tokyo Medical and Dental University, Tokyo, Japan). These cells were cultured in RPMI 1640 medium containing 10% FCS, 10 mM HEPES, 2 mM l-glutamine, 0.1 mg/ml penicillin and streptomycin, and 50 μM 2-ME.
Generation of anti-mouse B7-H3 mAbs
The anti-mouse B7-H3 mAbs were generated by immunizing Sprague Dawley rats with B7-H3-Ig, consisting of the extracellular domain (aa 1–242 of mouse B7-H3) (14) linked to the Fc portion of mouse IgG2a, emulsified in CFA (Difco). Three days after the final immunization, lymph node (LN) cells were fused with P3U1 myeloma cells. After hypoxanthine-aminopterin-thymidine selection, hybridomas (MJ8, rat IgG2b/κ, and MJ18, rat IgG1/κ) producing anti-B7-H3 mAb were selected by their reactivity to mouse B7-H3-transfected cells, but not to parental cells by flow cytometry, and then cloned by limiting dilution. The mAbs were purified from ascites by the caprylic acid and ammonium sulfate precipitation method, and purity was verified by SDS-PAGE analysis.
Flow cytometric analysis
Cells (0.5–1 × 106) were first preincubated with unlabeled anti-CD16/32 mAb to avoid nonspecific binding of Abs to FcγR, and then incubated with biotinylated mAbs. After washing with PBS twice, the cells were incubated with PE-labeled streptavidin. Anti-CD86 (GL1) and anti-B7-H4 (clone 9) mAbs, rat IgG isotype control, and PE-labeled streptavidin were purchased from eBioscience. The hybridomas producing mAb against B7-1 (1G10) were purchased from American Type Culture Collection. Anti-B7RP-1 (HK5.3), anti-B7-H1 (MIH6), and anti-B7-DC (TY25) mAbs were prepared, as described previously (22, 23). After washing with PBS twice, the stained cells (live gated on the basis of forward and side scatter profiles and propidium iodide exclusion) were analyzed on a FACSCalibur (BD Biosciences), and data were processed using the CellQuest program (BD Biosciences).
In vitro T cell proliferation assay
CD4+ T cells were purified from the spleen of DO11.10/Rag-2−/− mice or BALB/c mice by passage through nylon wool column (Wako Biochemicals) and by using autoMACS columns with CD4+ T cell isolation kit (Miltenyi Biotec), according to the manufacturer’s instructions. Purified CD4+ T cells (1 × 105/well) from DO11.10/Rag-2−/− mice were cultured with bone marrow-derived DCs (BMDCs; 2 × 104/well) and 2 μM OVA323–339 peptide in the presence or absence of anti-B7-H3 mAbs (10 μg/ml). Purified CD4+ T cells (1 × 105/well) from BALB/c mice were stimulated with immobilized anti-CD3 (2C11) mAb (0.5 μg/ml) and mouse rB7-H3 (rmB7-H3) (2 μg/ml; R&D Systems) in the presence or absence of anti-CD28 (PV-1) mAb (0.5 μg/ml) and anti-B7-H3 mAbs (10 μg/ml). Anti-CD28 (PV-1) mAb was provided by R. Abe (Tokyo University of Science, Chiba, Japan) and C. June (University of Pennsylvania, Philadelphia, PA). To assess proliferative responses, the cultures were pulsed with [3H]thymidine (0.5 μCi/well; GE Healthcare) for the last 6 h of a 48-h culture and harvested on a Micro 96 Harvester (Molecular Devices). Incorporated radioactivity was measured on a microplate beta counter (Micro β Plus; Wallac).
Induction of allergic airway inflammation and mAb treatment
Groups of 10 mice were sensitized by i.p. injection of 10 μg of OVA (Sigma-Aldrich) with 2 mg of alum (Pierce) (OVA/alum) on days 0 and 14. On days 22, 24, 26, and 28, the mice inhaled aerosolized 30 ml of 1% OVA in PBS (OVA/PBS). The aerosol was generated by nebulizer (NE-U07; Omron). Some groups of mice were i.p. injected with 300 μg of anti-B7-H3 mAb (MJ18) or control rat IgG (Sigma-Aldrich) on days 0, 2, 4, 7, 11, 14, 16, 18, 21, 24, and 27. Negative control animals were sensitized by i.p. injection of PBS with alum (PBS/alum) on days 0 and 14, and inhaled PBS in a similar manner. Two days after the last OVA inhalation, AHR was measured and bronchoalveolar lavage fluid (BALF) was collected, as described below. To examine the effect of anti-B7-H3 mAb in the induction phase, mice were injected with 300 μg of anti-B7-H3 mAb or control rat IgG on days 0, 2, 4, 7, 11, 14, 16, and 18. To examine the effect in the effector phase, mice were injected with the same dose of anti-B7-H3 mAb or control rat IgG on days 21, 24, and 27.
Measurement of AHR
AHR was measured by methacholine (WAKO)-induced airflow obstruction. Mice were placed into whole-body plethysmographs (Buxco Research Systems) interfaced with computers using differential pressure transducers. Airway resistance is expressed as: enhanced pause (Penh) = ((Te/0.3Tr) − 1) × (2Pef/3Pif), where Te = expiratory time (s), Tr = relaxation time (s), Pef = peak expiratory flow (ml), and Pif = peak inspiratory flow (ml/s). Increasing doses of methacholine were administered by nebulization (for 2 min), and Penh were calculated over the subsequent 5 min.
Characterization of BALF
After AHR measurement, the trachea was cannulated with a polyethylene tube through which the lungs were gently lavaged with 0.5 ml of PBS containing 10% FCS four times (2 ml total of BALF). The total number of cells was determined by Turk dye exclusion. Differential cell count was performed by staining of cytospins with Diff-Quik (Sysmex International Reagents).
Histological analysis of lung sections
Lungs were removed from mice that were not subjected to the bronchial lavage procedure. Lungs were inflated and fixed by intratracheal instillation of 20% buffered formalin (pH 7.4) at a constant pressure of 25 cm H2O for 24 h. After routine processing of successive dehydration, the lungs were embedded in paraffin and sectioned in a sagittal plain. Sections of 5 μm thickness were stained with H&E or periodic acid-Schiff (PAS) and Alcian blue (AB) as a measure of mucus production. To quantify the infiltration of eosinophils in the lung tissue, cell counting was performed in a blinded manner based on a 5-point scoring system, as follows: 0, no eosinophil; 1, few eosinophils; 2, a ring of eosinophils one cell layer deep; 3, a ring of eosinophils two to four cells deep; 4, a ring of eosinophils more than four cells deep. Scoring was performed in at least 15 different fields for each lung section. Mean scores were obtained from six animals. Airway mucus levels were determined by counting PAS- or AB-positive cells as a percentage of total epithelial cells in a blinded manner, according to methods described (24).
Stimulation of bronchial LN cells in vitro
After AHR measurement, bronchial LN cells were isolated and pooled, and cultured in 96-well flat-bottom microculture plates at a density of 6 × 105 cells/well in the presence or absence of the indicated doses of OVA. To assess proliferative responses, the cultures were pulsed with [3H]TdR (0.5 μCi/well) for the last 6 h of a 72-h culture and harvested on a Micro 96 Harvester. Incorporated radioactivity was measured on a microplate beta counter. To determine the production of cytokines, cell-free supernatants were collected at 72 h and assayed for IL-4, IL-5, and IL-10 by ELISA using OptEIA kits (BD Biosciences), IL-13 using Quantikine Immunoassay (R&D Systems), and IFN-γ using Mouse IFN-γ ELISA Ready-SET-Go! kit (eBioscience), according to the manufacturer’s instructions.
Induction of DCs and macrophages from bone marrow cells and immunization
BMDCs were prepared by culturing bone marrow cells from BALB/c mice, according to the procedure developed by Lutz et al. (25). Briefly, bone marrow cells (2 × 106/100 mm bacteriological petri dish) were cultured in 10 ml of RPMI 1640 medium containing 10% FCS, 10 mM HEPES, 2 mM l-glutamine, 0.1 mg/ml penicillin and streptomycin, and 50 μM 2-ME, and supplemented with 20 ng/ml GM-CSF (eBioscience). On day 3, another 10 ml of RPMI 1640 medium containing 20 ng/ml GM-CSF was added, and on day 6 half of the culture supernatant was collected and centrifuged, and the cell pellet was resuspended in 10 ml of fresh RPMI 1640 medium containing 20 ng/ml GM-CSF and given back into the original plate. On day 8, CD11c+ BMDCs were isolated by incubation with anti-CD11c-coupled magnetic beads and positive selection over an autoMACS column, according to the manufacturer’s instructions. The purity was checked by flow cytometric analysis (>98% CD11c+). For Ag pulsing, 100 μg/ml OVA was added to the cultures, and then the cells were further cultured overnight. OVA-pulsed BMDCs were washed in PBS and immunized (3 × 105 cells) into the hind footpads of BALB/c mice (n = 5). Mice were i.p. administrated with 300 μg of anti-B7-H3 mAb (MJ18) or control rat IgG on days 0, 2, and 5 after immunization, and popliteal LNs were harvested on day 8. In another experiment, BALB/c mice (n = 5) were immunized s.c. in the neck with OVA/alum and i.p. administrated with 300 μg of anti-B7-H3 mAb or control rat IgG on days 0, 2, and 4 after immunization, and cervical LNs were harvested on day 7. LN cells were pooled from five mice in each group and restimulated with the indicated doses of OVA at 6 × 105 cells/0.2 ml in 96-well plates. The proliferative response and cytokine production were measured, as described above.
Bone marrow-derived macrophages (BMMacs) were also prepared by culturing bone marrow cells from BALB/c mice. Bone marrow cells (5 × 106/100 mm bacteriological petri dish) were cultured in 10 ml of RPMI 1640 medium with 50 ng/ml M-CSF (Wako). On day 3, nonadherent cells were aspirated, and 10 ml of RPMI 1640 medium containing 50 ng/ml M-CSF was added, and on day 6 adherent cells on the bottom of the plate were collected by 0.1% EDTA/PBS (>98% CD11b+). Purified BMMacs and BMDCs were stimulated with anti-CD40 (FGK45) mAb (5 μg/ml), IFN-γ (20 ng/ml), or IL-4 (20 ng/ml) at 37°C for 24 h.
Significant differences between two experimental groups were analyzed by unpaired Student’s t test. The results are expressed as the mean ± SEM. Values of p < 0.05 were considered significant.
Establishment of anti-mouse B7-H3 mAbs
We immunized Sprague Dawley rats with B7-H3-Ig chimera protein and screened the hybridomas producing mAb that reacted with B7-H3 transfectants, but not parental cells. Two mAbs, designated MJ8 and MJ18, were selected. As represented in Fig. 1,A, MJ8 reacted strongly with B7-H3-transfected cells (B7-H3/L5178Y and B7-H3/P815), but not with parental L5178Y and P815 cells. MJ18 bound to B7-H3-transfected cells weakly, but not to parental cells. Both MJ8 and MJ18 failed to bind to the other B7 family-transfected cells (B7-1/P815, B7-2/P815, B7RP-1/L5178Y, B7-H1/L5178Y, B7-DC/L5178Y, and B7-H4/P815) (Fig. 1,B), indicating that MJ8 and MJ18 are specific for B7-H3. We also examined the expression of B7-H3 on BMDCs and BMMacs, which were prepared by culturing bone marrow cells with GM-CSF or M-CSF, respectively, by staining with MJ8. As shown in Fig. 1,C, although B7-H3 expression was not found on unstimulated BMDCs and BMMacs, it was detectable on both BMDCs and BMMacs after stimulation with anti-CD40 mAb or IFN-γ for 24 h, but not with IL-4. Because B7-H3 expression was inducible on BMDCs, we further tested whether the anti-B7-H3 mAbs would affect the stimulation of Ag-specific CD4+ T cells by BMDCs. Purified CD4+ T cells from DO11.10/Rag-2−/− mice were cultured with BMDCs and 2 μM OVA323–339 peptide in the presence of anti-B7-H3 mAbs or control IgG. As shown in Fig. 2,A, the addition of OVA323–339 peptide induced CD4+ T cell proliferation, and this proliferation was not affected by MJ8. In contrast, addition of MJ18 significantly inhibited the CD4+ T cell proliferation. Similar activities of MJ8 and MJ18 were observed when purified CD4+ T cells from BALB/c mice were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of rmB7-H3 (Fig. 2 B). No difference in CD4+ T cell proliferation was observed when rmB7-H3 was added to the culture with anti-CD3 mAb alone. However, rmB7-H3 significantly enhanced CD4+ T cell proliferation stimulated by anti-CD3 and anti-CD28 mAbs. This enhancement was not affected by addition of control IgG or MJ8. In contrast, the addition of MJ18 mostly abrogated the enhancement by rmB7-H3. Collectively, our in vitro results indicate a substantial involvement of B7-H3 in the CD4+ T cell proliferative responses in vitro, which can be blocked by MJ18.
Anti-B7-H3 mAb treatment suppresses the development of asthmatic responses
To explore the contribution of B7-H3 to the pathogenesis of asthma, we administrated anti-B7-H3 mAb (MJ18) or control rat IgG from day 0 to 27 to a murine model of asthma. BALB/c mice were sensitized by injection of OVA with alum on days 0 and 14, and then challenged by inhalation of aerosolized OVA on days 22, 24, 26, and 28. On day 30, the control IgG-treated mice developed a typical asthmatic phenotype characterized by AHR to methacholine (Fig. 3,A) and accumulation of eosinophils in BALF (Fig. 3,B). Histological examination showed massive infiltration of eosinophils around the bronchioles (Fig. 3, C and F), and mucus overproduction in the bronchioles (Fig. 3, D, E, G, and H). In contrast, development of AHR (Fig. 3,A), accumulation of eosinophils (Fig. 3, B, C, and F), and overproduction of mucus (Fig. 3, D, E, G, and H) were greatly reduced in the anti-B7-H3-treated mice.
The amelioration of asthma by anti-B7-H3 mAb might result from modulation of OVA-specific CD4+ T cell responses. To address this possibility, bronchial LN cells were prepared on day 30, and proliferative response and Th2 cytokine production (IL-4, IL-5, and IL-13) against various doses of OVA were assessed. As represented in Fig. 3,I, OVA-specific proliferative response was almost abrogated in LN cells from the anti-B7-H3-treated mice as compared with those from the control IgG-treated mice. The production of IL-4, IL-5, and IL-13 was also significantly reduced in the anti-B7-H3-treated mice as compared with the control IgG-treated mice (Fig. 3 J). These results indicate that B7-H3 plays a critical role in the development of allergic asthma and Th2 responses in this model.
Effect of anti-B7-H3 mAb treatment during induction or effector phase of allergic asthma
Although the above results indicated a critical contribution of B7-H3 to the development of allergic asthma, it was not clear whether B7-H3 played a role during the induction phase of pathogenic Th2 cell development or during the effector phase of pathogenic Th2 cell migration and activation in the lung. We next examined whether B7-H3 played a role during the induction phase or the effector phase of allergic asthma. OVA-immunized BALB/c mice were treated with anti-B7-H3 mAb or control IgG at the time of OVA sensitization from day 0 to 18 for the induction phase or from day 21 to 27 before the first OVA inhalation for the effector phase. Administration of anti-B7-H3 mAb at the induction phase significantly inhibited development of AHR (Fig. 4,A), accumulation of eosinophils in BALF (Fig. 4,B), and eosinophilia and mucus overproduction in the lung (Fig. 4, C–H). In addition, anti-B7-H3-treated mice showed significantly reduced OVA-specific proliferative response and production of Th2 cytokines (IL-4, IL-5, and IL-13) in LN cells as compared with control IgG-treated mice (Fig. 4, I and J). In contrast, anti-B7-H3 mAb treatment at the effector phase did not inhibit development of AHR (Fig. 5,A), accumulation of eosinophils, and mucus overproduction in the lung (Fig. 5, B–H), or OVA-specific proliferative response and Th2 cytokine production in LN cells (Fig. 5, I and J). These results indicate a critical contribution of B7-H3 to the induction phase of allergic asthma, but B7-H3 dose not play a major role in the effector phase, including the migration and activation of pathogenic Th2 cells in the lung.
Anti-B7-H3 mAb treatment inhibits priming Th2 response by OVA/alum
To further evaluate whether B7-H3 plays a critical role in priming of CD4+ T cells, BALB/c mice were immunized s.c. in the neck with OVA/alum and treated with anti-B7-H3 mAb or control IgG on days 0, 2, and 4. Cervical LN cells were harvested 7 days after immunization and restimulated in vitro with OVA, and proliferative response and Th2 cytokine production (IL-4, IL-5, and IL-10) were assessed. As represented in Fig. 6,A, OVA-specific proliferative response was significantly reduced in LN cells from the anti-B7-H3-treated mice as compared with those from the control IgG-treated mice. Production of Th2 cytokines was also significantly reduced in the anti-B7-H3-treated mice as compared with the control IgG-treated mice (Fig. 6 B). We also examined the effect of anti-B7-H3 mAb treatment on the induction of regulatory T cells, which were determined by flow cytometric analysis of CD4+CD25+ Foxp3+ cells in LN cells. The anti-B7-H3-treated mice exhibited no significant difference in the frequency of CD4+CD25+ Foxp3+ cell population within total CD4+ T cells (1.64 ± 0.12%) as compared with the control IgG-treated mice (1.70 ± 0.26%).
Anti-B7-H3 mAb treatment inhibits priming of CD4+ T cell responses by OVA-pulsed BMDCs
We further tested the effect of anti-B7-H3 mAb treatment on DC-induced CD4+ T cell responses. BMDCs were prepared by culturing bone marrow cells from BALB/c mice with GM-CSF for 8 days, and than pulsed overnight with OVA. A total of 3 × 105 BMDCs was subsequently injected into the hind footpads of syngeneic mice, which were treated with anti-B7-H3 mAb or control rat IgG on days 0, 2, and 5. Popliteal LN cells were harvested on day 8 and restimulated with OVA in vitro. Consistent with the previously published results (26), LN cells from the control IgG-treated mice produced IL-4, IL-5, IL-10, and IFN-γ when restimulated with OVA in vitro (Fig. 6,C). In contrast, LN cells from the B7-H3-treated mice produced significantly reduced levels of IL-4, IL-5, IL-10, and IFN-γ (Fig. 6 C). An addition of anti-B7-H3 or control IgG in the cultures had no effect (data not shown). Taken together, our present results suggest that B7-H3 plays a critical role in the induction phase of asthmatic response, particularly the priming of Th2 response by DCs.
To explore the contribution of B7-H3 to the development of allergic asthma, we first generated anti-mouse B7-H3 mAbs (MJ8 and MJ18), which bound to B7-H3 cDNA transfectants, but not to those expressing the other B7 family molecules (B7-1, B7-2, B7RP-1, B7-H1, B7-DC, and B7-H4). Moreover, MJ18, but not MJ8, significantly inhibited CD4+ T cell proliferation stimulated by BMDCs or anti-CD3 and anti-CD28 mAbs with rmB7-H3. These results indicate that MJ18 used in this study is specific for mouse B7-H3 and can interrupt the interaction between B7-H3 and its putative receptor. The anti-B7-H3 mAb-treated mice showed a substantial reduction of the OVA-induced asthmatic responses. Moreover, the administration of anti-B7-H3 mAb during the induction phase effectively ameliorated the asthmatic responses, although it was not effective during the effector phase. In vitro restimulation of draining LN cells showed that the anti-B7-H3 mAb treatment significantly reduced OVA-specific proliferative response and production of Th2 cytokines (IL-4, IL-5, and IL-13). These results suggest that B7-H3 plays its major role in the development of pathogenic Th2 cells during the induction phase, but not in the recruitment or activation of Th2 cells in the lung during the effector phase. In support of this notion, we also found that the anti-B7-H3 mAb treatment inhibited the priming of OVA-reactive Th2 cells induced by OVA/alum immunization or OVA-pulsed BMDC immunization. Collectively, these results suggest that the most critical role of B7-H3 in the asthmatic responses is to facilitate the priming of pathogenic Th2 cells, and that B7-H3 delivers a positive signal to CD4+ T cells leading to enhanced proliferation and cytokine production.
Several recent studies, however, indicated that B7-H3 might have inhibitory functions in certain circumstances. Under Th1-, but not Th2-polarizing conditions, B7-H3-deficient mice developed more severe airway inflammation than wild-type mice (16). B7-H3-deficient mice also developed experimental autoimmune encephalomyelitis 2 days earlier than wild-type mice, but disease severity and incidence were comparable to wild-type mice (16). These results suggested that B7-H3 could be involved in the suppression of Th1-mediated immune responses. Thus, the present suppression of asthmatic response by anti-B7-H3 mAb might be due to an augmentation of Th1 responses. However, this possibility seems unlikely because the anti-B7-H3 mAb treatment inhibited not only Th2-type cytokines, but also Th1-type IFN-γ production in LN cells from the mice primed by OVA-pulsed BMDCs. Moreover, IFN-γ was not detectable in OVA-restimulated LN cells from the anti-B7-H3-treated mice in Figs. 3 and 4 (data not shown). Therefore, the anti-B7-H3 mAb treatment inhibited Th2 development, but this did not result in a dramatic shift to Th1 responses. These results also suggest that the anti-B7-H3 mAb treatment potentially has an inhibitory effect on Th1-mediated immune responses. Further studies are required to address this possibility using Th1-polarized disease models.
The immunization of BALB/c mice with OVA/alum preferentially induces a Th2 response and high levels of serum anti-OVA IgG1 and IgE Abs. The blockade of B7-H3 abrogated the development of asthmatic responses and Th2 responses in LN cells. However, it should be noted that the anti-B7-H3 mAb treatment did not affect the serum levels of anti-OVA IgG1 and IgE even when mice were treated with anti-B7-H3 during both induction and effector phases (data not shown). These results indicate that B7-H3 does not contribute to the Ab production in the OVA-induced asthma model. We previously indicated that the blockade of B7RP-1, which is another member of the B7 family, by neutralizing anti-B7RP-1 mAb, abolished the development of CXCR5+ CD4+ T cells and germinal center B cells in the spleen in response to Ag immunization (27). The chemokine receptor CXCR5 confers responsiveness to B lymphocyte chemokine (CXCL13), which is produced by follicular stroma cells in the spleen, LN, and Peyer’s patches (28, 29). CXCR5 is constitutively expressed by circulating B cells and is required for their migration into B cell follicles in the secondary lymphoid organs (30, 31). A subset of CD4+ T cells also expresses CXCR5, which mediates their migration to the B cell follicles, where they provide cognate help to B cells (32, 33, 34, 35). Thus, CXCR5+ CD4+ T cells are referred to as follicular B helper T cells and differ from Th1 and Th2 cells (35, 36). The differential role of B7-H3 in Th2 response and Ab production may be explained by differential contributions of Th2 cells and CXCR5+ CD4+ T cells. Further studies are needed to address this possibility.
In conclusion, a potent inhibition of the inflammatory response in mouse model of asthma was observed with anti-B7-H3 mAb administration. B7-H3 appears to play a critical role in the development of pathogenic Th2 cells, and thus represents a novel target for intervention of allergic asthma.
The authors have no financial conflict of interest.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Abbreviations used in this paper: AHR, airway hyperreactivity; AB, Alcian blue; BALF, bronchoalveolar lavage fluid; BMDC, bone marrow-derived dendritic cell; BMMacs, bone marrow-derived macrophages; DC, dendritic cell; LN, lymph node; PAS, periodic acid-Schiff; Penh, enhanced pause; rmB7-H3, mouse rB7-H3.


Coronella austriaca, also known as the "smooth snake," was one of the species in the study. Image credit: Wikimedia Commons
Conducting a global study of an entire sub-order of species is not a simple proposition. It requires huge amounts of data, conducted by field researches in locations around the world, that spans a decade or more. As a result, such studies are able to provide only a slight indication of trends.
But sometimes, the findings are so consistent, so compelling, that they cannot be ignored.
Vierpa aspis aspis was one of the many species found to be in decline. Image credit: Wikimedia Commons
Such was the case with a recent study of global snake populations. Combing through data on 17 snake populations covering eight species around the world, researchers observed an "alarming" decline in global populations.
Chris Reading, who led the project, explained:
This is the first time that data has been analyzed in this way, and what we've shown is that in different parts of the world we seem to have this steep decline in a short period.
He went on to say that "it surprised us when we realised what we were looking at."
Another species in the study, Python regiusalso showed declines. Image credit: quantumdtell/Flickr
The data sets showed steep declines eight of the 17 populations—some by more than 90 percent. Only one population showed signs of an increasing population.
Declines were observed even in protected areas, indicating that something other than habitat loss may be a driver. Climatic events, the team proposed, could be one reason, though it is impossible to determine without further research.
A similar study of global amphibian populations eventually led researchers to identify a chytridiomycosis epidemic as the major cause of declines of those species.
"The purpose of this paper was to say 'this is what we've found', and to say to other herpetologists 'now go and look at your own data'," Reading explained, ""But I think that with so many populations in different places showing decline, it's more than co-incidence."


Professor Luke O'Neill from Trinity College Dublin, Ireland, identified the protein in 2001. The protein, known as Mal, alerts the immune system to respond against invading bacteria. Now, Professor Adrian Hill from the Wellcome Trust Centre for Human Genetics, University of Oxford, UK, has shown that there are two variants of Mal in humans and that the combination of these variants determines how the immune system responds.
The results of the study, funded by the Wellcome Trust, Science Foundation Ireland, Irish Health Research Board and the Agency for Science, Technology and Research, Singapore, are published in the April edition of Nature Genetics this week.
"Mal is in effect an alarm system for the immune system," explains Professor O'Neill. "When the body is infected with the malaria parasite or other germs, a set of sensors called 'toll-like receptors' (TLRs) lock onto the intruder. TLRs relay the detection via Mal, which wakes up the immune system to mobilise and defend us."
However, working with patients in Kenya, the Gambia, Vietnam and the UK, Professor Hill and his team showed that there are two common variants of the protein, one which allows the immune system to work normally, the other resulting in too strong a stimulation. A person will carry a combination of two copies of the protein, one from the mother and one from the father.
"If you have the overactive type, you are twice as likely to succumb to infection because your immune system goes into overdrive, often leading to severe forms of the disease, in a manner akin to ‘friendly fire’," explains Professor Hill, a Wellcome Trust Principal Research Fellow. "Similarly, if you have two copies of the less active form, the body does not fight the infection and you get the disease. The optimum situation is to have one copy of each variant, giving a balanced system, sufficient to mount a response, but not overly activating."
The researchers found that having the overactive Mal doubled the risk of disease, with a four times greater risk of severe malaria in some populations. Malaria and TB account for over five million deaths per year in the developing world, particularly amongst children.
"We hope that a drug that modulates the balance of Mal variants might prevent disease in those who are at greater risk," says Professor O'Neill. "Our next step is to work towards developing such drugs."
The research has been welcomed by Dr Mark Walport, Director of the Wellcome Trust, which funds research into diseases of the developing world such as malaria and TB, mainly through its major overseas programmes.
"Malaria and TB present a major challenge to the health of people in the developing world," says Dr Walport. "Particularly given the recent rise in the number of cases of drug-resistant strains, it is essential that we understand how the immune system responds to infection if we are to develop novel treatments."
The researchers also believe that the findings may provide a valuable insight into how dysfunctional immune systems can lead to non-infectious diseases, specifically autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
Craig Brierley | alfa
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
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Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
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- Note that this small randomized trial found that postmenopausal women with mild cognitive impairment who received hormone replacement therapy had better cognitive assessment scores at 2 years than those who received placebo.
- Be aware that the statistical significance only emerged after adjustment for APOE genotype -- larger studies will be needed to confirm the observed effect.
Hormone therapy slowed cognitive decline in postmenopausal women with mild cognitive impairment, according to results of a small, randomized, placebo-controlled clinical trial.
In 35 postmenopausal women with mild cognitive impairment followed for 2 years, those who received hormone therapy scored significantly better than a placebo group on the Montreal Cognitive Assessment (mean difference 3.85, 95% CI -0.46 to 8.16, P=0.043) and the Mini-Mental State Examination (mean difference 3.26, 95% CI 0.04-6.48, P=0.0319), reported researchers led by Byung-Koo Yoon, MD, of the Sungkyunkwan University School of Medicine in Seoul, Korea.
The treatment group did not score significantly better on the Alzheimer's disease Assessment Scale. In addition, there were no significant differences between the treatment and placebo groups in assessments of depression or quality of life, which are often associated with declines in cognitive function, Yoon's group wrote online in the Journal of the North American Menopause Society.
The therapy used in the study consisted of percutaneous estradiol (E2) gel and oral micronized progesterone (MP4). "To our knowledge, this is the first study to report the therapeutic potential of percutaneous E2 gel combined with oral MP4 in mild cognitive impairment," the researchers said. "All tests for general cognition ... showed obvious exacerbation over 24 months in the placebo group, whereas they remained unchanged in the MHT [menopausal hormone therapy] group, implying that MHT has potential beneficial effects on cognition."
Better scores on the Montreal Cognitive Assessment in the treatment group became evident at 18 months. Better function as measured by this test could have meaningful clinical implications because it is to date the most sensitive tool for assessing global cognitive ability in mild cognitive impairment, the researchers said.
The prospective, double-blind trial included 35 postmenopausal Korean women with mild cognitive impairment. Their mean age was 70 (range 57-82). All received the dementia drug donepezil (Aricept) for ethical reasons, the researchers explained. The initial dose of donepezil was 2.5 mg/d for the first week, which was then doubled for the next 4 weeks, and then increased up to 10 mg/d if tolerated. All participants were assessed for apolipoprotein E (APOE) genotype, an established risk factor for Alzheimer's and poor cognitive function.
The women were randomized to receive 100 mg/day of MP4 plus E2 percutaneous gel 0.1% applied to the forearm before sleep or lookalike placebos. The starting dose of E2 was 0.5 mg/d and was increased monthly up to 2 mg/day if well tolerated. Participants were followed for 2 years, and cognitive function was assessed every 6 months.
The primary outcome was change in cognitive function as measured by the Korean versions of the Montreal Cognitive Assessment, the Mini-Mental State Examination, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Quality of life, depression, and the ability to perform activities of daily living were also assessed every 6 months with various tests.
During the course of the study, nine of 17 participants in the placebo group progressed to have dementia (53%) versus eight of 18 patients in the treatment group (44%). However, in the initial univariate analysis, the investigators found no significant differences in cognitive function between the treatment and placebo groups. The differences became significant only after the team adjusted for Apo E genotype.
Adverse events were more common in the treatment group (n=17; 90%) versus the placebo group (n=7; 39%). The most common events were vaginal spotting/bleeding, breast pain/change, and other genital discomfort, which are typical side effects of hormone therapy. No cardiovascular events, cancers, or deaths occurred in the treatment group, the investigators said.
Hormone therapy might improve cognitive function in a variety of ways, Yoon et al explained. The treatment boosts cholinergic functions in the basal forebrain, and evidence suggests it leads to synaptic plasticity in the prefrontal cortex and hippocampus, and may decrease the production of amyloid plaques.
Asked for her opinion, JoAnn Pinkerton, MD, executive director of the North American Menopause Society, called the results promising, but emphasized they are preliminary and need to be confirmed: "Based on the small numbers of women, hormone therapy (transdermal estradiol and progesterone) improved cognitive function in women who were early cognitive changers," she said via email. "Larger trials are needed to evaluate the impact of hormone therapy use before the full onset of Alzheimer's disease to determine if there is a role for hormone therapy in preventing or slowing Alzheimer's disease."
Limitations of the study, the researchers said, included the small sample size and the fact that the participants were all Korean, so it is possible that the results are not generalizable to other populations. "Additional large-scale, long-term trials are needed to confirm our findings and eventually to determine whether MHT could delay or diminish mild cognitive impairment progression to dementia in postmenopausal elders."2 comments


I went trillium hunting at Warwoman Dell. I did find a few just starting to come up but, none with flowers on them. One had a bud. On the right is a photo of a clump of Round Leaved Violets that was growing along the trail. Trail conditions are fairly poor as several trees have fallen across it during the winter. In a couple of weeks I expect the trilliums to really begin their season of blooms.


Background: Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMφ) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematode Nippostrongylus brasiliensis, in the presence or absence of Plasmodium chabaudi chabaudi malaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection. Results: We observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection. Conclusion: P. c. chabaudi co-infection altered both local and lymph node Type 2 immune activation due to migration of N. brasiliensis larvae. Given recent work from other laboratories showing that N. brasiliensis-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.
All Science Journal Classification (ASJC) codes


The Anzali Ramsar Convention wetland is located in an ecologically and economically important region in Iran. The wetland is largely surrounded by agriculture, natural forests and rangelands (approximately 36% and 63%, respectively). Urban areas consist of less than 1% of the total area. Urban land use produces the highest rates of nutrient transfer into the lake as TN, TP and BOD5 equal to 24, 2.4 and 79 Kg/ha/year, respectively, whilst, natural land use produces the lowest rate as 10, 1.3 and 27 kg/ha/year. These results will inform the future sustainable management of this important wetland in this ever increasingly water stressed region in Iran.
|Number of pages||5|
|Journal||Bulletin of Environmental Contamination and Toxicology|
|Publication status||Published - Feb 2010|
- Ramsar wetlands
- Transfer model


Vijay G. Sankaran, MD, PhD
Associate Professor at Boston Children's Hospital
2018 NYSCF – Robertson Stem Cell Investigator Alumnus
MD, PhD, Harvard University
Residency and Clinical Fellowship, Dana-Farber Cancer Institute, Boston Children’s Hospital; Postdoctoral Studies, Whitehead Institute, Broad Institute
Dr. Sankaran is an Associate Professor of Pediatrics at Boston Children’s Hospital, where his laboratory uses human genetics to better understand hematopoiesis and how it goes awry in human disease. In particular, he seeks to gain molecular insight into how hematopoiesis varies in humans both in health and disease, and to develop improved therapies for a variety of blood disorders. He completed his residency and clinical fellowship at Dana-Farber Cancer Institute and Boston Children’s Hospital, and his postdoctoral studies at the Whitehead and Broad Institutes.
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When it comes to cannabis, there is a belief that the potency of a high is directly correlated with higher levels of THC. However, it is important to note that the strength of weed does not solely depend on THC content. In this article, we will delve into some of the key factors beyond THC levels that contribute to a strain’s potency levels.
Exploring the Entourage Effect: Beyond THC
While THC is undoubtedly the most well-known cannabinoid compound in cannabis, it does not work alone in producing its psychoactive effects. The combination of cannabinoids and other compounds found in cannabis creates what experts refer to as the entourage effect. This collaborative interaction alters how different compounds interact with each other, ultimately influencing the experience of the high.
Rather than solely focusing on percentages of THC, experienced cannabis enthusiasts and connoisseurs seek out strains that are rich in multiple cannabinoids, such as CBD, CBN, CBG, and THCV, among others. Each cannabinoid affects our receptors differently, leading to an interplay of effects that can vary significantly from person to person.
Terpenes. More Than Just Aromatics
Terpenes play a role not only in providing distinct flavors and aromas to different strains but also contribute significantly to their overall characteristics and effects. However, these aromatic compounds not only contribute significantly to the benefits of cannabis, but they also bind to different receptors in our brains and bodies. This interaction plays a role in enhancing or mitigating the effects of cannabinoids like THC. For example, myrcene is a terpene commonly found in cannabis strains known for promoting relaxation and sedation. On the other hand, pinene enhances alertness. By considering the different terpene profiles rather than just focusing on THC concentration, users can tailor their desired experience based on specific strains.
The Importance of Genetic Variations in Cannabis Strains
The composition of a cannabis strain is another factor that determines its potency. Even if two strains have similar THC levels, they may not offer the same effects or possess the same strength. This variation in experience can be attributed to factors such as terpene profiles and the entourage effect mentioned earlier. The way these compounds interact within each strain is what ultimately shapes the experience of the high. As a result, two strains with THC concentrations can produce entirely different effects due to variations in their genetic makeup.
The Impact of Consumption Methods
The method of consuming cannabis also plays a key role in how it’s metabolized by the body and experienced by individuals. Smoking allows cannabinoids to enter the bloodstream quickly, leading to an immediate onset but shorter duration of effects. On the other hand, edibles offer a more consistent release of effects that can last longer, although it may take more time to feel their impact. When looking for a more potent high, it is crucial to consider the method of consumption. Trying out different techniques allows individuals to find the consumption method that suits them best.
Personal Factors – Unique Reactions
When it comes to different strains of cannabis, personal factors play a major role as well. Each person’s unique biological makeup affects how they respond to cannabis. Variables like metabolism, tolerance levels, previous experiences, mental state, and overall health all influence how an individual’s body interacts with cannabis. What might be too strong for one person may not provide adequate effects for another. Hence, recognizing these factors is important when choosing strains and consuming cannabis products.
While THC is often seen as the primary indicator of potency in cannabis strains, it does not provide the complete picture. Knowledgeable consumers understand that multiple cannabinoids, compositions, and genetic variations among strains matter more than just high THC percentages. By understanding these elements, from terpenes contributing to flavor and aroma to reactions influenced by genetic differences, consumers can make informed decisions when seeking a stronger or more potent cannabis experience. Keep in mind that it’s not just about the numbers. Instead, it involves acknowledging the intricacies of cannabis and discovering the strain that best suits your requirements and preferences. So, when you think about the strength of your marijuana, dig deeper than THC and explore the captivating range of compounds that influence our cherished herb.


Introduction: The Androctonus australis hector (Aah) venom is a complex of high and low molecular weight components. Scorpion envenoming. Toxicol Appl Pharmacol. Feb 1;(3) Epub Nov Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in. Androctonus australis hector insect toxin also known as AaHIT is a scorpion toxin which affects voltage-gated sodium channels. Four different insect toxins, Other Names: AaHIT or AaIT.
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There are many pathways autoxidation of glucose, polyol pathway, protein glycation, formation of advanced glycation products… by which hyperglycemia can increase the ROS production.
Obtained results suggest that the inhibition of voltage-gated sodium channels before venom injection seems to induce a decrease androctonus australis hector blood glucose in hyperglycemic model and androctonus australis hector prevent some disturbances induced by hyperglycemia.
Immunity — Nutrition — Cancer Citation: Description[ edit ] Androctonus australis is a medium-sized scorpion which can grow up to 10 centimeters in length.
Fab was more effective than F ab' 2 for preventing early symptoms of envenomation, whatever their route of administration. Intraperitoneal injection of F ab' 2 and Androctonus australis hector was similar for the prevention of the delayed symptoms, even after a late administration.
Fab was more effective than F ab' 2 in the inhibition of airway resistance, independent of the route and time of administration. Androctonus australis Linnaeus, Cardiac dysfunctioning androctonus australis hector pulmonary edema following scorpion envenomation.
Androctonus australis - Wikipedia
Chest, 4pp. Gifttier Informationsdienst on A. This scorpion is a medium sized scorpion which can get up to 10 cm in androctonus australis hector.
Journal of Insect Physiology.
- The Scorpion Files - Androctonus australis (Buthidae)
- Androctonus australis hector insect toxin - Wikipedia
- Androctonus australis hector venom effects on oxidative stress biomarkers in experimental model
The Journal of Neuroscience.


Q.Why Leucadendron Safari Sunset Leaves Turning Brown?
I got these very young Leucadendron plants two months ago. I followed the nursery guy told me and water them once every 3-4 days. He told me to water this frequency because the plants are still so young. I also followed what I was told using cactus soil mixed with all plant soil. The water seems drain fast. All three plants are slowly growing while started to have brown leaves. One of them has a whole branch turning brown. Please see the pictures. Would anyone tell me what did I do wrong? Too much water? Thank you.
Certified GKH Gardening Expert
These plants will not tolerate wet soils. Even when they are young, they need to dry out very thoroughly between waterings. Unless your area is prone to extreme drought (Think African desert) you won't need to water at all.
From here, you will want to halt watering, completely, and treat with a fungicide.
These articles will help:


We all know we are supposed to exercise and eat well to maintain good health, but another factor that is essential to our health is sleep. Adults should sleep for 7 or more hours each night for optimal health. However, more than 1/3 of U.S. adults get less than that. The obvious consequences of lack of sleep are feeling tired, both physically and mentally, and having difficulty with thinking and memory. However, there are other more serious side effects of chronic sleep loss.
Lack of sleep can affect our health, putting us at an increased risk of heart disease, heart attacks, stroke, diabetes, and obesity. It can also play a role in our mental health as lack of sleep increases the risk of depression. In addition to those conditions, lack of sleep makes our immune system weaker. In fact, people who sleep less than 7 hours per night are 3 times more likely to get the common cold. Sleep apnea, which is a sleep disorder in which breathing repeatedly stops and starts, can also cause these health conditions and should be treated.
We also tend to look older when we have a lack of sleep as our body releases more stress hormones. On the other hand, we don’t release enough growth hormone, which helps grow and repair our muscles, skin, and bones. Not only does our body repair itself at night, but our brain does as well. While we sleep our brain forms new pathways to help us learn and remember new information, but it also flushes toxins out and gets rid of connections we don’t need.
Also, sleep can help reduce pain. Studies show that when we have sleep loss, we can tolerate less pain. On the other hand, a good night’s sleep has been shown to be as helpful as pain medication for pain relief. Obviously, sleep is a very important part of good health.
In addition getting more sleep for better health, we can also improve our quality of sleep by practicing “sleep hygiene.” This includes napping no longer than 30 minutes during the day, avoiding caffeine and alcohol close to bed time, exercising (but not too close to bedtime), avoiding heavy and rich foods right before bed, and making sure the sleep environment is comfortable. You can also make sure the temperature is below 67 degrees, the lights are off, you are not watching TV in bed, and maintain a regular sleep schedule.
If you have concerns regarding your sleep, you can always contact your primary care physician.