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Several preclinical and clinical studies have shown the immunomodulatory role exerted by prebiotics in regulating the immune response. In this review, we describe the mechanistic and clinical studies that decipher the cell signaling pathways implicated in the process. Prebiotic fibers are conventionally known to serve as substrate for probiotic commensal bacteria that release of short-chain fatty acids in the intestinal tract along with several other metabolites. Subsequently, they then act on the local as well as the systemic immune cells and the gut-associated epithelial cells, primarily through G-protein-coupled receptor-mediated pathways. However, other pathways including histone deacetylase inhibition and inflammasome pathway have also been implicated in regulating the immunomodulatory effect. The prebiotics can also induce a microbiota-independent effect by directly acting on the gut-associated epithelial and innate immune cells through the Toll-like receptors. The cumulative effect results in the maintenance of the epithelial barrier integrity and modulation of innate immunity through secretion of pro- and anti-inflammatory cytokines, switches in macrophage polarization and function, neutrophil recruitment and migration, dendritic cell and regulatory T-cell differentiation. Extending these in vitro and ex vivo observations, some prebiotics have been well investigated, with successful human and animal trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in health endpoints across populations. This review discusses scientific insights into the association between prebiotics, innate immunity and gut microbiome from in vitro to human oral intervention.
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Microbioma Gastrointestinal , Microbiota , Probióticos , Animais , Humanos , Imunidade Inata , PrebióticosRESUMO
Although deregulated circulatory miRNA signatures during diabetes have been identified for some years now, the effects of such miRNAs on several target tissues are not yet thoroughly investigated. The skin that is nourished by components present in the circulation exhibits several notable abnormal features during diabetes. We, therefore, hypothesized that such altered circulatory miRNA levels might be critical in the onset and progression of impaired skin health during diabetes. RNA sequencing from blood samples of normal and type 2 diabetic human subjects identified 9 upregulated and 19 downregulated miRNAs. miR-98-5p was significantly downregulated and its overexpression down-regulated PPP1R15B levels in HaCaT cells and this was prevented by the miR-98-5p inhibitor. This was validated in human primary epidermal keratinocytes and further supported by a dual reporter luciferase assay of the PPP1R15B 3'UTR where miR-98-5p significantly decreased the luciferase activity which was prevented in the presence of the miRNA inhibitor and by mutation in the miRNA binding site. By targeting PPP1R15B, miR-98-5p increases levels of p-eIF2α, BiP and CHOP. Consequently, there was induction of apoptosis accompanied with decreased proliferation in the presence of miR-98-5p. Conversely, miR-98-5p inhibition alone inhibited apoptosis and promoted proliferation. Taken together, our data suggest that by targeting PPP1R15B, miR-98-5p induces apoptosis and decreases proliferation. As opposed to this since circulatory miR-98-5p levels are decreased in diabetes, we believe that this decrease in the circulation that feeds the skin layers might be a major contributor of hyperproliferation as seen in the skin during diabetes.Abbreviations: miRNAs: MicroRNAs; PPP1R15B: PPP1R15B: Protein Phosphatase 1 Regulatory Subunit 15B; TGFßR1: Transforming Growth Factor Beta Receptor 1; ER: Endoplasmic Reticulum; Bip: Binding Immunoglobulin Protein; Chop: CCAAT-enhancer-binding protein homologous protein; p-eIF2α: Eukaryotic Translation Initiation Factor 2a; Bax: Bcl2-associated X protein; Bcl-2: B-cell CLL/lymphoma 2; PCNA: Proliferating Cell Nuclear Antigen; K5: Cytokeratin 5; qRT-PCR: Quantitative Real-Time PCR; ESCC: Oesophageal squamous cell carcinoma; HCC: Hepatocellular carcinoma; CTHRC1: Collagen triple helix repeat containing 1; SALL4: Sal-like protein 4; TNFα: Tumour Necrosis Factor alpha; PGC-1ß: Peroxisome Profilerator-activated receptor-γ coactivator-1ß; IGF2BP1: Insulin-like growth factor 2 mRNA binding protein 1.
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Apoptose/genética , Diabetes Mellitus Tipo 2/genética , Regulação Neoplásica da Expressão Gênica , Queratinócitos/metabolismo , MicroRNAs/genética , Proteína Fosfatase 1/genética , Interferência de RNA , Adulto , Linhagem Celular Tumoral , Diabetes Mellitus Tipo 2/metabolismo , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Fator de Transcrição CHOP/metabolismoRESUMO
Two natural homogalacturonan (HG) pectins (MW ca. 20 kDa) were isolated from green tea based on their immunomodulatory activity. The crude tea polysaccharides (TPS1 and TPS2) were obtained from green tea leaves by hot water extraction and followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water soluble polysaccharides (TPS1-2a and TPS1-2b) were obtained from TPS1 after purification with gel permeation, which gave a higher phagocytic effect than TPS2. A combination of composition, methylation and configuration analyses, as well as NMR (nuclear magnetic resonance) spectroscopy revealed that TPS1-2a and TPS1-2b were homogalacturonan (HG) pectins consisting of a backbone of 1,4-linked α-D-galacturonic acid (GalA) residues with 28.4% and 26.1% of carboxyl groups as methyl ester, respectively. The immunological assay results demonstrated that TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing activity in HL-60 cells.
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Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Pectinas/química , Pectinas/farmacologia , Chá/química , Linhagem Celular , Humanos , Fatores Imunológicos/isolamento & purificação , Metilação , Pectinas/isolamento & purificação , Fagocitose/efeitos dos fármacosRESUMO
Eosinophilia develops in reactive environment such as allergy, parasitic infections and in hypereosinophilic syndrome [HES]. Activated eosinophils are accompanied by a wide variety of inflammatory response due to release of toxic inflammatory mediators, which may result in severe tissue/organ damage at the site of eosinophilic infiltrations, due to degranulation. The factor responsible for the detrimental effect of activated circulatory eosinophils is an area less explored. In the present study, we determined the serum cytokine milieu of eosinophilic and control subjects, and also investigated the change in the pattern of cytokine released under mitogen stimulation. Increased level of various pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IL-5 and IL-17 was detected in serum and culture supernatants of endotoxin stimulated white blood cells [WBCs] of eosinophilic subjects compared to control population. It was observed that endotoxin exposure in WBCs of eosinophilic subjects, led to increased release of IL-17, produced by TH17 subset of T-cell, contributing towards eosinophilic exuberations, in vitro. We observed non-specific lysis by eosinophils under such inflammatory milieu and synergistic eosinophilic activity in presence of IL-17 and IL-5 in combination. Taken together, our findings provide vital insight on TH17 lymphocyte mediated activation of eosinophils, via differential cytokine regulation, which play an important role in hypereosinophilic systemic inflammation.
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Eosinofilia/sangue , Eosinofilia/imunologia , Eosinófilos/imunologia , Interleucina-17/imunologia , Células Th17/imunologia , Adulto , Feminino , Humanos , Inflamação/sangue , Interleucina-17/sangue , Interleucina-1beta/sangue , Interleucina-5/sangue , Interleucina-6/sangue , Lipopolissacarídeos/imunologia , Masculino , Fator de Necrose Tumoral alfa/sangueRESUMO
Background: Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Materials and Methods: Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. Results: End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Conclusions: Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.
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Background: Primary scarring alopecias (PSAs) are a rare group of dermatological disorders with overlapping clinical features. They result in permanent hair loss and significant psychological morbidity. Aims: To analyze the clinico-epidemiology of PSAs of the scalp, along with clinico-pathological correlation. Methods: We conducted a cross sectional, observational study including 53 histopathologically confirmed cases of PSA. Clinico-demographic parameters, hair care practices, and histologic characteristics were noted and statistically analyzed. Results: Among 53 patients (mean age 30.9 ± 8.1 years, M: F 1:1.2, median duration 4 years) with PSA, lichen planopilaris (LPP) was most common (39.6%, 21/53), followed by pseudopelade of Brocq [30.2%, 16/53], discoid lupus erythematosus (DLE) [16.9%, 9/53], and non-specific scarring alopecia (SA) (7.5%, 4/53), while central centrifugal cicatricial alopecia (CCCA), folliculitis decalvans, and acne keloidalis nuchae (AKN) accounted for 1 case each. Forty-seven patients (88.7%) demonstrated predominant lymphocytic inflammatory infiltrate, while basal cell degeneration and follicular plugging were the commonest histological changes. Perifollicular erythema and dermal mucin deposition were noted in all patients with DLE (both P < 0.05). Nail involvement (P = 0.004) and mucosal involvement (P = 0.8) were more common in LPP. Single alopecic patches were characteristic of DLE and CCCA. Hair care practices (non-medicated shampoo > oil) had no significant association with the subtype of PSA. (P = 0.4). Conclusion: PSAs are a diagnostic challenge for dermatologists. Thus, histology and clinico-pathological correlation should be performed in all cases for proper diagnosis and treatment.
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OBJECTIVE: To review the in-patient (IP) management patterns and 30-day outcomes of patients admitted with macroscopic haematuria (MH) over a 1-year-period in a single-institution, aiming to clarify management for such cases in the future. METHODS: Retrospective cohort study was conducted on all patients admitted with MH in a single-institution over 1-year, excluding patients not requiring an overnight stay. A case note review was performed for patient demographics, MH investigations, and management. RESULTS: A total of 120 patients were admitted with MH over a span of 1-year. 89% (107/120) were males, with an average age of 78 years (36-97 years), an average ASA of 3, mean length-of-stay (LOS) was 5 days (1-31days) and 68% (82/120) had pre-existing urological conditions. 62% (74/120) required bladder irrigation for a mean duration of 3 days (1-16days). 10% (12/120) required an emergency rigid cystoscopy and washout to manage the bleeding, of which 4% (5/12) had malignancy noted. Over 8% (10/120) patients discharged had unplanned readmissions within 30 days. The 1-year mortality for this cohort was 23% (28/120) of which 21% (6/28) died within 30 days from discharge. CONCLUSION: IP MH affects a vulnerable patient cohort. There is no specific pathway guiding the inpatient management of MH; therefore, research is required to produce standardized pathways for managing MH, considering the high-risk patient cohort, the prolonged LOS, and high 1-year mortality rate.
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Hematúria , Urologia , Idoso , Cistoscopia , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Hematúria/terapia , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Estudos RetrospectivosRESUMO
The effect of a tea fortified with five herbs selected from Indian traditional medicine (Ayurveda) for their putative immunoenhancing effect (Withania somnifera, Glycyrrhzia glabra, Zingiber officinale, Ocimum sanctum and Elettaria cardamomum) on innate immunity was investigated. Ex vivo natural killer (NK) cell activity was assessed after consumption of fortified tea compared with regular tea in two independent double-blind intervention studies. Both studies were conducted in India with healthy volunteers (age >or= 55 years) selected for a relatively low baseline NK cell activity and a history of recurrent coughs and colds. In a pilot study conducted with 32 volunteers, the consumption of Natural Care tea significantly improved the NK cell activity of the volunteers in comparison with a population consuming regular tea. These results were validated in an independent crossover study with 110 volunteers. Data from these two studies indicate that regular consumption of the tea fortified with Ayurvedic herbs enhanced NK cell activity, which is an important aspect of the (early) innate immune response to infections.
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Células Matadoras Naturais/efeitos dos fármacos , Ayurveda , Plantas Medicinais/imunologia , Chá/imunologia , Idoso , Linhagem Celular , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Imunidade Inata , Índia , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Type 2 diabetes (T2D) is a complex metabolic syndrome characterized by insulin dysfunction and abnormalities in glucose and lipid metabolism. The gut microbiome has been recently identified as an important factor for development of T2D. In this study, a total of 102 subjects were recruited, and we have looked at the gut microbiota of prediabetics (PreDMs) (n = 17), newly diagnosed diabetics (NewDMs) (n = 11), and diabetics on antidiabetic treatment (KnownDMs) (n = 39) and compared them with healthy nondiabetics (ND) (n = 35). Twenty-five different serum biomarkers were measured to assess the status of diabetes and their association with gut microbiota. Our analysis revealed nine different genera as differentially abundant in four study groups. Among them, Akkermansia, Blautia, and Ruminococcus were found to be significantly (P < 0.05) decreased, while Lactobacillus was increased in NewDMs compared to ND and recovered in KnownDMs. Akkermansia was inversely correlated with HbA1c and positively correlated with total antioxidants. Compared to ND, there was increased abundance of Megasphaera, Escherichia, and Acidaminococcus and decreased abundance of Sutterella in KnownDMs. Among many taxa known to act as community drivers during disease progression, we observed genus Sutterella as a common driver taxon among all diabetic groups. On the basis of the results of random forest analysis, we found that the genera Akkermansia and Sutterella and that the serum metabolites fasting glucose, HbA1c, methionine, and total antioxidants were highly discriminative factors among studied groups. Taken together, our data revealed that gut microbial diversity of NewDMs but not of PreDMs is significantly different from that of ND. Interestingly, after antidiabetic treatment, the microbial diversity of KnownDMs tends to recover toward that of ND.IMPORTANCE Gut microbiota is considered to play a role in disease progression, and previous studies have reported an association of microbiome dysbiosis with T2D. In this study, we have attempted to investigate gut microbiota of ND, PreDMs, NewDMs, and KnownDMs. We found that the genera Akkermansia and Blautia decreased significantly (P < 0.05) in treatment-naive diabetics and were restored in KnownDMs on antidiabetic treatment. To the best of our knowledge, comparative studies on shifts in the microbial community in individuals of different diabetic states are lacking. Understanding the transition of microbiota and its association with serum biomarkers in diabetics with different disease states may pave the way for new therapeutic approaches for T2D.
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INTRODUCTION: Trophic ulcer is a dreaded complication of leprosy. Secondary infection compounds the damage to the already neglected ulcer. AIMS: To find out the bacterial pathogens in the isolates from trophic ulcers of leprosy and to find the drug sensitivity of the aerobic isolates so as to start a suitable antibiotic therapy. METHODOLOGY: An institution-based, cross-sectional study done over a period of 2 years. Swab was taken from the deeper part of the ulcer. It was put on a suitable culture media. Bacteriological profile was determined and antibiogram was done subsequently. RESULTS: Sixty patients with trophic ulcer secondary to leprosy were screened, among which all were screened for aerobic isolates and 38 were screened for anaerobic isolates. Among the aerobic isolates, 88% of patients were culture-positive. The most common organism was Staphylococcus aureus (37.7%), followed by Pseudomonas aeruginosa (22.64%), Proteus mirabilis (15.09%), Escherischia coli (13.2%), Klebsiella (9.43%). Maximum overall sensitivity was seen with amikacin (93.1%) and linezolid (89.65%). Maximum overall resistance was noted with cotrimoxazole (58.62%) and coamoxiclav (51.72%). Among the 38 patients cultured for anaerobic isolates, 17 were culture-positive for anaerobic organisms. Isolates showing Peptococcus were 6 (15.7%), purely Peptostreptococcus were 4 (10.5%), purely bacteroides were 3 (7.8%), and mixed growths were 4 (10.5%). CONCLUSION: Secondary bacterial infection is quite common in leprosy trophic ulcers. The most common organism was Staphylococcus aureus. Isolates were mostly sensitive to amikacin and linezolid and resistant to cotrimoxazole and coamoxiclav. Anaerobic isolates were not uncommon, with Peptococcus being the most common among them.
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INTRODUCTION: Self-medication behavior appears to be a commonplace; and when it is ignorant it may prove dangerous. On the other hand, dispensing errors and consequent adverse outcomes, though not too uncommon, are seldom reported. We report here a case of methotrexateinduced acute vesico-bullous eruptions in a patient of psoriasis who indulged in self-medication and was wrongfully dispensed higher doses of methotrexate. CASE DESCRIPTION: A 50-year-old man was diagnosed with psoriasis two years back and advised tablet methotrexate 20 mg once weekly and folic acid supplementation. He experienced symptoms remission after 8 weeks of treatment and preferred to discontinue the medication. As the psoriatic lesions reappeared four weeks ago, he attended a retail pharmacy for refill of the two-year old prescription. He was obliged by the man in the counter who wrongfully dispensed the medicine and the patient consumed methotrexate 10 mg twice daily. On the 20th days, the patient experienced erythematous, vesico-bullous lesions spread all over the body including both limbs and scalp, with oral mucosal involvement without any history of fever, and with mildly deranged liver function, and presented to the dermatology OPD of a tertiary hospital. He was admitted and treated with injection glucocorticoid and leucovorin. He responded well and completely recovered in a week. A 'probable' causality was adjudged for this serious adverse event by both WHO-UMC scale and Naranjo's algorithm. The reaction was moderately severe (Hartwig's scale) and it was definitively preventable (modified Schumock-Thornton scale). CONCLUSION: This case report highlights the hazard of uninformed Self-medication and irresponsible dispensing behavior resulting in serious drug-related injury.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Erros de Medicação/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Automedicação/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/tratamento farmacológicoRESUMO
Placement of decorative tattoo on the skin may lead to various immunological, infective, and coincidental complications. Inoculation of human papillomavirus leading to development of verruca is an uncommon complication of tattoos. The present report highlights the development of verruca vulgaris, developing after 2 years of tattooing in a young male.
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Human keratinocytes (HaCaT) were exposed to UV (A+B) (UVA-350-400 mJ/cm2 and UVB-30 mJ/cm2) which induces apoptosis as evidenced by MTT assay, DNA laddering, Bax and Fas up-regulation. UV induced apoptotic conditioned media (6 h or earlier) did not cause apoptosis in unexposed cells. However, treatment with conditioned medium collected post UV exposure (1 h) induced Bax in unexposed cells as observed by RT-PCR. The induction of cell death was initiated by conditioned medium collected 12 h after UV exposure and the extent of death was increased progressively when conditioned medium collected 24 or 72 h post UV exposure was used. Medium collected 24 h after UV exposure also increased mitochondrial membrane permeability as determined by rhodamine uptake. Conditioned medium induced apoptosis did not involve reactive oxygen species (ROS) unlike UV induced apoptosis indicating that the apoptosis pathway could be different. Interestingly, at high dilution apototic conditioned medium did not induce apoptosis but actually protected cells from UV insult. The role of nerve growth factor (NGF) in UV induced bystander effects are also discussed.
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Apoptose , Efeito Espectador , Dano ao DNA , Queratinócitos/fisiologia , Raios Ultravioleta , Permeabilidade da Membrana Celular , Meios de Cultivo Condicionados , Formazans/farmacologia , Regulação da Expressão Gênica , Humanos , Mitocôndrias , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Sais de Tetrazólio/farmacologia , Regulação para CimaRESUMO
The prevalence of metabolic syndrome is increasing rapidly across the globe. Though the prevalence of the disease is similar in population of upper middle income and high income countries, the age of affected population is lower in upper middle income countries. This is attributed to genetic as well as changing life style factors. The contributing factors for type 2 diabetes range from genetic/epigenetic disposal, intra uterine nutrition, dietary pattern to sedentary lifestyle. The role of the gut microbiota in metabolic disorders is increasingly gaining importance. Several studies have reported significant difference in the profile of the gut microbiota in Caucasian population considering obese and type 2 diabetic populations while limited number of studies are available on populations from the developing world. The metabolites from the gut microbes contribute to the gut barrier integrity and a compromised barrier leads to leakage of inflammatory mediators into systemic circulation and hence increases insulin resistance. Attempts have been made at correcting metabolic syndrome through dietary changes by altering the gut microbiota with some success. This report is an attempt to explain the hypothesis of compromised nutrition altering the gut microbiota, gut metabolites, gut barrier function, systemic inflammation and hence insulin response.
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Diabetes Mellitus Tipo 2 , Comportamento Alimentar , Microbioma Gastrointestinal , Estilo de Vida , Países Desenvolvidos , Países em DesenvolvimentoRESUMO
Differential gene regulation during UVB induced apoptosis of human keratinocyte cell line (HaCaT) has been investigated. Rapid amplification of polymorphic DNA (RAPD)-PCR was done to identify novel/unique genes in the purified apoptotic and non-apoptotic populations. Two genes were identified and cloned in pGemT vector. One of these genes (apgene-1) was upregulated in UV induced apoptotic cells and in the non apoptotic cells exposed to UV. The other gene (apgene-2) was not detected in apoptotic cells but expressed in non-apoptotic/non necrotic cells that had been exposed to UV. The presence of apgene-1 mRNA was not detected in camptothecin induced apoptotic as well as non apoptotic cells. Apgene-2 was not detected in camptothecin induced apoptotic cells but expressed in non-apoptotic/non necrotic cells. This data indicates differential regulation of these two genes during UV and chemical induced apoptosis in human keratinocytes. Additionally, since apgene-2 was upregulated in the non necrotic/non apoptotic population could be involved in protection.
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A rapid in vitro method has been developed to screen skin allergens and irritants. It has been shown by others that allergens induce the secretion of interleukin (IL)-1 betaby dendritic cells and macrophages, which are known antigen-presenting cells present in blood, and that irritants induce the secretion of IL-1 alphaby the same cells. We have shown that the allergens nickel, chromium, isoeugenol, and dinitrofluoro benzene induce the secretion of IL-1 betaat levels that are two- to threefold higher than those of controls and that the nonallergens and irritants sodium dodecyl sulfate, Tween-20, acetic acid, sodium hydroxide, and dimethyl sulfoxide fail to induce such a response. All the chemical allergens tested induced the secretion of IL-1 alphaat concentrations two- to fivefold higher than those of controls, depending on the concentration and the particular irritant. Allergen-induced T-cell proliferation has also been demonstrated by the expression of IL-2 as well as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide reduction (MTT) assay (10-50% more than control). All the allergens and irritants caused cytotoxicity at higher doses, as indicated by the release of lactate dehydrogenase. This method can be used to differentiate the allergens from the irritants in a simple and convenient manner.
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Type 2 Diabetes is a complex disease with multifactorial pathogenesis. The interplay between genes and lifestyle changes complicates the etiology of the disease. In spite of growing number of attempts to unravel the mechanism of this metabolic disease, the molecular nature of type 2 Diabetes is not fully understood. The discovery of a new class of non-coding RNAs, micro RNAs and their role in regulation of gene expression have paved the way for better understanding of disease pathogenesis. Increasing number of evidences suggest crucial role of miRNAs in insulin resistance and ß cell dysfunction, which are the two main features of type 2 Diabetes. This review summarizes the role of miRNA in elicitation and progression of type 2 Diabetes.
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Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Epigênese Genética , MicroRNAs/metabolismo , Animais , Linfócitos B/patologia , Diferenciação Celular , Diabetes Mellitus Tipo 2/genética , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Resistência à InsulinaRESUMO
Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in 'probable' category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.
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Aim The objective of the study was to identify the association if any, of inflammatory markers (adiponectin and IL-6) with fasting glucose in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) people in Indian population. Methods Total 162 volunteers were distributed into 3 groups (normoglycemic, individuals with impaired fasting glucose, and hyperglycemic) as per ADA criterion. The blood chemistry parameters were analyzed and serum adiponectin and IL-6 levels were measured by ELISA. Results Significant reduction was observed in serum adiponectin level in hyperglycemic and impaired fasting glucose population compared with normoglycemic population. Significant reduction in adiponectin was also observed in impaired fasting glucose group compared with hyperglycemic group. Similarly significant increase was also observed in IL-6 level in hyperglycemic and impaired fasting glucose groups compared with normoglycemic group. Conclusions From our data it can be summarized that there is a significant change in both adiponectin (reduction) and IL-6 (increase) levels in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) population in Indian population. There is a significant but gradual change during the progression of healthy toward diabetic population via pre-diabetic condition.