Equal remission rates and reduced length of hospital stay with twice-daily repetitive transcranial magnetic stimulation (rTMS) for major depression - A large naturalistic retrospective cohort association study.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital. METHODS: A total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). The a priori primary outcome measure was remission rate as measured by pre and post treatment HAMD-17 scores. Length of hospital stay was a secondary post hoc outcome adopted due to the importance to cost of acute psychiatric care. RESULTS: Remission rates were similar across groups, with 44.9% and 45.4% for twice daily and daily rTMS groups respectively, although these may be confounded by patient expectations, other treatments and medication changes given the naturalistic setting. The length of hospital stay was 10.11 days and 18.44 days for twice daily and daily rTMS respectively - the twice daily rTMS length of hospital stay was 45.1% shorter 95% CI [38.7% - 51.56%]. Dropout rates were high; Twenty-seven (24.77%) twice daily participants dropped out before 20 sessions were completed, and 35 (34.65%) of daily participants. CONCLUSIONS: Twice daily 10 Hz left sided rTMS remission outcomes were similar to traditional once daily rTMS but required a shorter length of hospital stay. This finding has substantial cost of care implications. If these findings are independently replicated, twice daily rTMS may become the standard of care for inpatient rTMS.

Critical review on emerging health effects associated with the indoor air quality and its sustainable management.

Indoor air quality (IAQ) is one of the fundamental elements affecting people's health and well-being. Currently, there is a lack of awareness among people about the quantification, identification, and possible health effects of IAQ. Airborne pollutants such as volatile organic compounds (VOCs), particulate matter (PM), sulfur dioxide (SO2), carbon monoxide (CO), nitrous oxide (NO), polycyclic aromatic hydrocarbons (PAHs) microbial spores, pollen, allergens, etc. primarily contribute to IAQ deterioration. This review discusses the sources of major indoor air pollutants, molecular toxicity mechanisms, and their effects on cardiovascular, ocular, neurological, women, and foetal health. Additionally, contemporary strategies and sustainable methods for regulating and reducing pollutant concentrations are emphasized, and current initiatives to address and enhance IAQ are explored, along with their unique advantages and potentials. Due to their longer exposure times and particular physical characteristics, women and children are more at risk for poor indoor air quality. By triggering many toxicity mechanisms, including oxidative stress, DNA methylation, epigenetic modifications, and gene activation, indoor air pollution can cause a range of health issues. Low birth weight, acute lower respiratory tract infections, Sick building syndromes (SBS), and early death are more prevalent in exposed residents. On the other hand, the main causes of incapacity and early mortality are lung cancer, chronic obstructive pulmonary disease, and cardiovascular disorders. It's crucial to acknowledge anticipated research needs and implemented efficient interventions and policies to lower health hazards.

Climate change and allergic diseases: An overview.

Climate change has been regarded as a threat to the human species on the earth. Greenhouse gasses are leading to increased temperatures on Earth besides impacting the humanity. These atmospheric conditions have shown to alter the release pattern of pollens and can change the timing and magnitude of pollen release with flowering plants. As pollen is responsible for respiratory allergies in humans, so climate change can adversely affect human health in susceptible individuals. In this review, we highlight the association between climate change, increased prevalence and severity of asthma, and related allergic diseases. Increased air pollution can alter the production of local and regional pollen. This altered pattern depends on bioclimatic parameters. As simulated with a pollen-release model and future bioclimatic data, warmer temperatures lead to an increased pollen count in some specific locations and for longer periods. Thus, anticipation of a future allergic disease burden can help public health agencies in planning to develop strategies in mitigating the unprecedented health challenges expected in future years.

Comprehensive health risk assessment of microbial indoor air quality in microenvironments.

The higher airborne microbial concentration in indoor areas might be responsible for the adverse indoor air quality, which relates well with poor respiratory and general health effects in the form of Sick building syndromes. The current study aimed to isolate and characterize the seasonal (winter and spring) levels of culturable bio-aerosols from indoor air, implicating human health by using an epidemiological health survey. Microorganisms were identified by standard macro and microbiological methods, followed by biochemical testing and molecular techniques. Sampling results revealed the bacterial and fungal aerosol concentrations ranging between (300-3650 CFU/m3) and (300-4150 CFU/m3) respectively, in different microenvironments during the winter season (December-February). However, in spring (March-May), bacterial and fungal aerosol concentrations were monitored, ranging between (450-5150 CFU/m3) and (350-5070 CFU/m3) respectively. Interestingly, Aspergillus and Cladosporium were the majorly recorded fungi whereas, Staphylococcus, Streptobacillus, and Micrococcus found predominant bacterial genera among all the sites. Taken together, the elevated levels of bioaerosols are the foremost risk factor that can lead to various respiratory and general health issues in additional analysis, the questionnaire survey indicated the headache (28%) and allergy (20%) were significant indoor health concerns. This type of approach will serve as a foundation for assisting residents in taking preventative measures to avoid exposure to dangerous bioaerosols.

Biological contaminants in the indoor air environment and their impacts on human health.

Indoor air environment contains a complex mixture of biological contaminants such as bacteria, fungi, viruses, algae, insects, and their by-products such as endotoxins, mycotoxins, volatile organic compounds, etc. Biological contaminants have been categorized according to whether they are allergenic, infectious, capable of inducing toxic or inflammatory responses in human beings. At present, there is a lack of awareness about biological contamination in the indoor environment and their potential sources for the spreading of various infections. Therefore, this review article examines the association of biological contaminants with human health, and it will also provide in-depth knowledge of various biological contaminants present in different places such as residential areas, hospitals, offices, schools, etc. Moreover, qualitative and quantitative data of bio-contaminants in various indoor environments such as schools, hospitals, residential houses, etc. have also been derived from the recent literature survey.

Seasonal variation and size distribution in the airborne indoor microbial concentration of residential houses in Delhi and its impact on health.

Exposure of microbial agents in the air of indoor dwellings is associated with effects on respiratory and general health. The current study was conducted in the urban area of Delhi Metropolis for the seasonal quantitative assessment of viable microbial indoor air quality. Bioaerosol measurement was conducted by using Anderson six stage impactor with cut-off diameters of 7.0, 4.7, 3.3, 2.1, 1.1, and 0.65 µm) throughout the all the seasons (April 2019 to March 2020). Meteorological parameters such as temperature and relative humidity were measured to check their effect on microbial survival. Air quality index data of the sampling area were recorded by DPCC air quality monitoring system, Ashok Vihar, Delhi. The highest (1654 ± 876.87 CFU/m3) and lowest (738 ± 443.59 CFU/m3) mean bacterial concentration in houses was recorded in August and December, respectively. Similarly, the highest fungal concentration (1275 ± 645.22 CFU/m3) was found in August and the lowest in (776 ± 462.46 CFU/m3) in January. Bacterial respirable fraction shows an irregular pattern in different seasons. In the case of fungi, the respirable fraction of 2.1 and 1.1 contributes more than 60% of total culturable bioaerosols in all seasons. Bacterial genera including Staphylococcus, Micrococcus, and Streptobacillus were most dominant, and Cladosporium, Aspergillus, Penicillium, and Alternaria were the most dominant fungal genera observed indoors. The results of this study suggest that higher respirable fungal fraction might penetrate deeper into the lungs and cause various health effects. A higher concentration of bioaerosols in outdoor areas than indoor shows that the source of indoor bioaerosols is outdoor air. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10453-021-09718-3.

Otological and Visual Implications of Diabetes Mellitus in North Indian Population.

The worldwide population of diabetic patients is increasing alarmingly with India claiming number one position. It causes irreversible damage to cochlear hair cells, vestibular apparatus, visual pathway, nephrons, nerves, if not checked in time. A total of 188 patients of diabetes mellitus were included in this prospective study. The patients underwent routine anamnesis, hearing handicap inventory and dizziness handicap inventory assessment along with clinical examination for audiological, vestibular, neurological and ophthalmological (fundoscopy) status. In our study a sensorineural hearing loss, retinopathy, neuropathy, vestibulopathy was seen in diabetic patients.

Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/ß-catenin signaling.

The hyperactivated Wnt/ß-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3ß independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/ß-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.

Gut permeability and mucosal inflammation: bad, good or context dependent.

Inflammatory bowel disease (IBD) is a multifactorial disease. A breach in the mucosal barrier, otherwise known as "leaky gut," is alleged to promote mucosal inflammation by intensifying immune activation. However, interaction between the luminal antigen and mucosal immune system is necessary to maintain mucosal homeostasis. Furthermore, manipulations leading to deregulated gut permeability have resulted in susceptibility in mice to colitis as well as to creating adaptive immunity. These findings implicate a complex but dynamic association between mucosal permeability and immune homeostasis; however, they also emphasize that compromised gut permeability alone may not be sufficient to induce colitis. Emerging evidence further supports the role(s) of proteins associated with the mucosal barrier in epithelial injury and repair: manipulations of associated proteins also modified epithelial differentiation, proliferation, and apoptosis. Taken together, the role of gut permeability and proteins associated in regulating mucosal inflammatory diseases appears to be more complex than previously thought. Herein, we review outcomes from recent mouse models where gut permeability was altered by direct and indirect effects of manipulating mucosal barrier-associated proteins, to highlight the significance of mucosal permeability and the non-barrier-related roles of these proteins in regulating chronic mucosal inflammatory conditions.

Claudin-7 expression induces mesenchymal to epithelial transformation (MET) to inhibit colon tumorigenesis.

In normal colon, claudin-7 is one of the highly expressed claudin proteins and its knockdown in mice results in altered epithelial cell homeostasis and neonatal death. Notably, dysregulation of the epithelial homeostasis potentiates oncogenic transformation and growth. However, the role of claudin-7 in the regulation of colon tumorigenesis remains poorly understood. Using a large colorectal cancer (CRC) patient database and mouse models of colon cancer, we found claudin-7 expression to be significantly downregulated in cancer samples. Most notably, forced claudin-7 expression in poorly differentiated and highly metastatic SW620 colon cancer cells induced epithelial characteristics and inhibited their growth in soft agar and tumor growth in vivo. By contrast, knockdown of claudin-7 in HT-29 or DLD-1 cells induced epithelial-to-mesenchymal transition (EMT), colony formation, xenograft-tumor growth in athymic mice and invasion. Importantly, a claudin-7 signature gene profile generated by overlapping the DEGs (differentially expressed genes in a high-throughput transcriptome analysis using claudin-7-manipulated cells) with human claudin-7 signature genes identified high-risk CRC patients. Furthermore, Rab25, a colon cancer suppressor and regulator of the polarized cell trafficking constituted one of the highly upregulated DEGs in claudin-7 overexpressing cells. Notably, silencing of Rab25 expression counteracted the effects of claudin-7 expression and not only increased proliferation and cell invasion but also increased the expression of p-Src and mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 that were suppressed upon claudin-7 overexpression. Of interest, CRC cell lines, which exhibited decreased claudin-7 expression, also exhibited promoter DNA hypermethylation, a modification associated with transcriptional silencing. Taken together, our data demonstrate a previously undescribed role of claudin-7 as a colon cancer suppressor and suggest that loss of claudin-7 potentiates EMT to promote colon cancer, in a manner dependent on Rab25.

Enzymatic hydrolysis: a method in alleviating legume allergenicity.

Legumes are involved in IgE mediated food allergy in many countries. Avoidance of allergenic food is the only way to avoid symptomatic reaction. The present study investigated the effect of enzymatic hydrolysis on the allergenicity of three legumes - kidney bean (Phaseolus vulgaris), black gram (Vigna mungo) and peanut (Arachis hypogaea). Soluble protein extracts of the study legumes were sequentially treated by Alcalase(®) and Flavourzyme(®). Allergenicity of hydrolysates was then determined by ELISA, immunoblot, stripped basophil histamine release and skin prick test (SPT). Hydrolysis resulted in the loss of all IgE binding fractions determined by immunoblot in the three legumes. Specific IgE binding in ELISA was reduced by 62.2 ± 7.7%, 87.1 ± 9.6% and 91.8 ± 7.2% in the hydrolysates of kidney bean, black gram and peanut, respectively (p < 0.01). The release of histamine was decreased significantly when sensitized basophils were challenged with hydrolysates as compared to raw extracts. Significant reduction in the biopotency of hydrolysates was also observed in SPT where only 1/10 kidney bean-sensitive individuals, 2/6 black gram-sensitive individuals and 1/7 peanut-sensitive individuals were found positive to their respective hydrolysates. In conclusion, enzymatic hydrolysis is effective in attenuating allergenicity of legume proteins and may be employed for preparing hypoallergenic food extracts.

Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis.

Expression of claudin-2, a tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Notably, claudin-2 has also been implicated in the regulation of intestinal epithelial proliferation. However, precise role of claudin-2 in regulating colonic homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic mice, that increased colonic claudin-2 expression augments mucosal permeability as well as colon and crypt length. Most notably, despite leaky colon, Cl-2TG mice were significantly protected against experimental colitis. Importantly, claudin-2 expression increased colonocyte proliferation and provided protection against colitis-induced colonocyte death in a PI-3Kinase/Bcl-2-dependent manner. However, Cl-2TG mice also demonstrated marked suppression of colitis-induced increases in immune activation and associated signaling, suggesting immune tolerance. Accordingly, colons from naive Cl-2TG mice harbored significantly increased numbers of regulatory (CD4(+)Foxp3(+)) T cells than WT littermates. Furthermore, macrophages isolated from Cl-2TG mouse colon exhibited immune anergy. Importantly, these immunosuppressive changes were associated with increased synthesis of the immunoregulatory cytokine TGF-ß by colonic epithelial cells in Cl-2TG mice compared with WT littermates. Taken together, our findings reveal a critical albeit complex role of claudin-2 in intestinal homeostasis by regulating epithelial permeability, inflammation and proliferation and suggest novel therapeutic opportunities.

First case report of anaphylaxis caused by Rajgira seed flour (Amaranthus paniculatus) from India: a clinico-immunologic evaluation.

The prevalence of food allergy is reported to be 3-4% in adults and about 6% in children. However food allergy across different countries accounts for 35-50 % all cases of anaphylaxis to foods. In the present study, we have reported a case of anaphylaxis to Amaranth grain (Amaranthus paniculatus) commonly known as Rajgira (Ramdana) in India. A 60 year old female suffered anaphylaxis after consuming Rajgira seed flour generally consumed during fasting. Food allergy to Amaranth seeds is not reported so far. The patient reported to hospital with complaints of itching in mouth, choking throat, redness and swelling of face and burning abdomen within 5 min of consuming Rajgira flour. Clinical and immunological investigations revealed SPT and oral challenge positivity beside high allergen specific IgE in the serum of the patient. Three IgE binding protein fractions were detected in roasted Rajgira seed flour extract which could be considered to be allergenically important for triggering anaphylaxis.

ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression.

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood-brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5-3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72-25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD.

Strengthening national health systems for improving efficiency of health service delivery in Nepal.

The success of Nepal's community-based health programmes in promoting maternal and child health has been achieved due to an overall improvement in service delivery facilities and health support systems. This article assesses the progress made by the Government of Nepal in improving health service delivery by introducing three key components: an improved health logistics management, facility-based maternal and neonatal health services, and decentralized health facility management.

Coagulanolide modulates hepatic glucose metabolism in C57BL/KsJ-db/db mice.

Increased hepatic glucose output is one of the major causes of fasting hyperglycemia in diabetic patients. In this study, we investigated the mechanism of action of coagulanolide on hepatic glucose, regulating enzymes in type 2 diabetic C57BL/KsJ-db/db (db/db) mice. Coagulanolide is an active component of Withania coagulans fruit. Oral administration of coagulanolide for 3 weeks decreases fasting blood glucose and plasma insulin significantly, and it improves glucose tolerance in the db/db mice group. The enzyme activity and protein expression of glucokinase and pyruvate kinase was significantly enhanced in coagulanolide-treated db/db group when compared with untreated one. On the other hand, activities and protein expression of fructose-1,6-bisphosphatase, glucose 6-phosphatase, phosphoenolpyruvate carboxykinase, and glycogen phosphorylase enzymes were significantly lowered in treated group. The treatment with coagulanolide also normalizes the concentrations of plasma cholesterol, triglyceride, free fatty acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the db/db mice. These findings suggested that the coagulanolide is useful in the control of fasting hyperglycemia in type 2 diabetes by regulating the production of hepatic glucose.

Anti-diabetic and anti-oxidative effects of 4-hydroxypipecolic acid in C57BL/KsJ-db/db mice.

Hypoglycemic effect of ethanol extracts of Peganum harmala (commonly known as 'Harmal') seeds has been reported on normal and streptozotocin-induced diabetic rats. In the present study, the authors determine anti-diabetic and anti-oxidative properties of 4-hydroxypipecolic acid (4-HPA) isolated from seeds of P. harmala in C57BL/KsJ-db/db mice. Twelve week old male mice were administered 50 mg/kg body weight (4-HPA suspension were made in 1% gum acacia) for the period of 10 days, and a significant reduction in the fasting blood glucose, plasma triglycerides (TG), cholesterol, free fatty acid, low-density lipoprotein-cholesterol and a significant increase in high-density lipoprotein-cholesterol level was observed with respect to vehicle-treated db/db mice. The anti-oxidant activity of 4-hydroxypipecolic acid was studied in liver and kidney tissues by assessing malondialdehyde levels for lipid peroxidation and enzyme activity of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Treatment of 4-HPA significantly lowered the lipid peroxidation in hepatic and renal tissue and increased the activity of CAT, GSH-Px and SOD in treated mice.

Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation.

Claudin-2 is a unique member of the claudin family of transmembrane proteins, as its expression is restricted to the leaky epithelium in vivo and correlates with epithelial leakiness in vitro. However, recent evidence suggests potential functions of claudin-2 that are relevant to neoplastic transformation and growth. In accordance, here we report, on the basis of analysis of mRNA and protein expression using a total of 309 patient samples that claudin-2 expression is significantly increased in colorectal cancer and correlates with cancer progression. We also report similar increases in claudin-2 expression in inflammatory bowel disease-associated colorectal cancer. Most importantly, we demonstrate that the increased claudin-2 expression in colorectal cancer is causally associated with tumor growth as forced claudin-2 expression in colon cancer cells that do not express claudin-2 resulted in significant increases in cell proliferation, anchorage-independent growth and tumor growth in vivo. We further show that the colonic microenvironment regulates claudin-2 expression in a manner dependent on signaling through the EGF receptor (EGFR), a key regulator of colon tumorigenesis. In addition, claudin-2 expression is specifically decreased in the colon of waved-2 mice, naturally deficient in EGFR activation. Furthermore, genetic silencing of claudin-2 expression in Caco-2, a colon cancer cell line, prevents the EGF-induced increase in cell proliferation. Taken together, these results uncover a novel role for claudin-2 in promoting colon cancer, potentially via EGFR transactivation.

Dust mites population in indoor houses of suspected allergic patients of South assam, India.

Background. In the present study, quality and quantity of indoor dust mites was evaluated at the residence of 150 atopic allergic patients from four different districts of South Assam. Methods. Suspected patients with case history of allergic disease were selected for indoor survey. Dust samples (500 mg) were collected from the selected patient's house and were analyzed using standard methods. Results. About 60% of the selected patients were found suffering from respiratory disorders and rest 40% from skin allergy. The dominant mites recorded from indoor dust samples were Dermatophagoides followed by Blomia, Acarus, and Cheyletus while Caloglyphus was recorded in least number. The distribution of mites on the basis of housing pattern indicates that RCC type of buildings supports maximum dust mite's population followed by Assam type (semi-RCC) buildings, and the lowest count was observed in wooden houses. Environmental factors like temperature, rainfall, and relative humidity are found to determine the indoor mite's population. Severity of allergic attack in some of the typical cases was found to be proportional to the allergen load of mites in the dust samples. Conclusions. The economic status, housing pattern, and local environmental factors determine the diversity and abundance of dust mites in indoor environment.

Antihyperglycaemic effect of an unusual amino acid (4-hydroxyisoleucine) in C57BL/KsJ-db/db mice.

The present report confirms the anti-hyperglycaemic and anti-dyslipidemic properties of 4-hydroxyisoleucine, an unusual amino acid isolated from Trigonella foenum-graecum seeds, for the first time in a well-characterised model of type II diabetes, i.e. db/db mice. 4-Hydroxyisoleucine, when given orally to these mice at 50 mg kg(-1) dose level, significantly (p < 0.05) declined their elevated blood glucose, plasma insulin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol levels and raised their declined plasma high-density lipoprotein-cholesterol level. These results indicate that 4-hydroxyisoleucine exhibits significant potential as an anti-diabetic agent by suppressing progression of type II diabetic states that is suggested by enhancement of insulin sensitivity and glucose uptake in peripheral tissue.