Drynaria quercifolia suppresses paracetamol­induced hepatotoxicity in mice by inducing Nrf-2.

Paracetamol is a popular and safe drug preferred by victims of pain or pyrexia; however, its overdose or abuse is a growing concern worldwide. Here the hepatoprotective effect of an ethnomedicinal plant Drynaria quercifolia against paracetamol­induced toxicity in murine model is demonstrated. This fern, native to tropical countries including the Northeast India, is used by local tribes to treat inflammatory conditions. Paracetamol 500 mg/kg body weight was orally administered on alternate days for a period of 21days to mimic a chronic overdose. Drynaria quercifolia acetone extract (DQA) treatment interspaced with paracetamol significantly decreased serum biomarkers of hepatotoxicity (ALT, AST and ALP) renal toxicity (urea, creatinine), lipid peroxidation level, histological damage in liver and kidney. The protein and mRNA expressions of the transcription factor, Nrf2, and its target antioxidant genes (SOD1, CAT and GST) as well as activities of these antioxidant enzymes were downregulated by paracetamol administration but significantly recovered following the DQA treatment (Tab. 3, Fig. 5, Ref. 31). Keywords: acetaminophen/paracetamol, Drynaria quercifolia, renal toxicity, hepatotoxicity, Nrf-2.

Serum lipoprotein ratios as markers of insulin resistance: a study among non-diabetic acute coronary syndrome patients with impaired fasting glucose.

BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION & CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

Tumor to tumor metastasis: adenocarcinoma of lung metastatic to meningioma.

Tumor-to-tumor metastasis (T2Tmets) is an established entity but often overlooked and underdiagnosed. Merely 84 such cases are reported in literature till date. The authors here describe a 65-year-old man presenting with first episode of focal seizure and incidentally turned out to be a case of adenocarcinoma of lung metastatic to a meningioma. The diagnosis of T2Tmets was based solely on histopathological criteria. Recent advent of brain imaging revolutionized its diagnosis and it has moved from the realm of thologists to that of radiologists. In our case, diagnosis was also established by immunohistochemistry.

Pharmacology and Ethnomedicinal Potential of Selected Plants Species from Apiaceae (Umbelliferae).

BACKGROUND: The Apiaceae or Umbelliferae is one of the largest families in terms of species representation in the plant kingdom. It is also a prominent family in the field of phytochemicals and pharmacology. The family is also quite prominent in the production of spices and condiments and food supplements in nutrition, aside from the potential of species in the family to induce apoptotic, antimicrobial, antitumor, and hepatoprotective activities. OBJECTIVE: This work presents a detailed structural elucidation and functional aspects of phytochemicals from the Apiaceae or Umbelliferae family. METHODS: Furthermore, the application of members of this family in traditional and modern pharmacology is emphasized. This review also highlights the linkage of phytochemicals used in the conventional system of medication for the development of novel therapeutics through a chain of pre-clinical and clinical trials. CONCLUSION: This study may represent a valuable step ahead in the clinical development of natural drugs for curing several ailments, including respiratory and virus-related diseases.

Vaccination saves lives: a real-time study of patients with chronic diseases and severe COVID-19 infection.

OBJECTIVES: This study aims to describe the demographic and clinical profile and ascertain the determinants of outcome among hospitalized coronavirus disease 2019 (COVID-19) adult patients enrolled in the National Clinical Registry for COVID-19 (NCRC). METHODS: NCRC is an on-going data collection platform operational in 42 hospitals across India. Data of hospitalized COVID-19 patients enrolled in NCRC between 1st September 2020 to 26th October 2021 were examined. RESULTS: Analysis of 29 509 hospitalized, adult COVID-19 patients [mean (SD) age: 51.1 (16.2) year; male: 18 752 (63.6%)] showed that 15 678 (53.1%) had at least one comorbidity. Among 25 715 (87.1%) symptomatic patients, fever was the commonest symptom (72.3%) followed by shortness of breath (48.9%) and dry cough (45.5%). In-hospital mortality was 14.5% (n = 3957). Adjusted odds of dying were significantly higher in age group ≥60 years, males, with diabetes, chronic kidney diseases, chronic liver disease, malignancy and tuberculosis, presenting with dyspnoea and neurological symptoms. WHO ordinal scale 4 or above at admission carried the highest odds of dying [5.6 (95% CI: 4.6-7.0)]. Patients receiving one [OR: 0.5 (95% CI: 0.4-0.7)] or two doses of anti-SARS CoV-2 vaccine [OR: 0.4 (95% CI: 0.3-0.7)] were protected from in-hospital mortality. CONCLUSIONS: WHO ordinal scale at admission is the most important independent predictor for in-hospital death in COVID-19 patients. Anti-SARS-CoV2 vaccination provides significant protection against mortality.

Amebic Liver abscess Complicated by Inferior Vena Cava Thrombosis: A Case Report.

Amebic liver abscess is the most common extraintestinal manifestation of infection with Entamoeba histolytica. It is a common disease, especially in endemic areas, but it is a rare cause of inferior vena cava (IVC) obstruction, with only a few cases appearing in the literature. The authors describe a case of amebic liver abscess in a patient who developed a rare vascular complication of inferior vena cava thrombosis. The case responded to conservative treatment and radiological intervention.

Impact of paper mill effluent on growth and development of certain agricultural crops.

The physico-chemical characteristics of paper mill industry effluent were measured and some were found to be above the permissible limits prescribed by Indian irrigation water standard. A study was conducted in pots to investigate the effects of different concentrations (10, 20, 30, 40, 50, 60, 70, 80 and 100%) of paper mill effluent on growth and production of rice, mustard and peafor three years. The study reveals that the paper mill effluent has deleterious effect on the growth of crop at higher concentrations. However, at lower concentration (viz. 10 to 40% in rice, 10 to 50% in mustard and 10 to 60% in pea) of effluent, beneficial impact on general welfare of the crops was noticed. Growth and development was increased with increasing the concentration of the effluent up to 30% in rice, 40% in mustard and 50% in pea. Investigation showed that the growth and production of rice, mustard and pea was found maximum at a concentration of 30, 40 and 50% effluent respectively.

Allospecific CD154+ T cells associate with rejection risk after pediatric liver transplantation.

Antigen-specific T cells, which express CD154 rapidly, but remain untested in alloimmunity, were measured with flow cytometry in 16-h MLR of 58 identically-immunosuppressed children with liver transplantation (LTx), to identify Rejectors (who had experienced biopsy-proven rejection within 60 days posttransplantation). Thirty-one children were sampled once, cross-sectionally. Twenty-seven children were sampled longitudinally, pre-LTx, and at 1-60 and 61-200 days after LTx. Results were correlated with proliferative alloresponses measured by CFSE-dye dilution (n = 23), and CTLA4, a negative T-cell costimulator, which antagonizes CD154-mediated effects (n = 31). In cross-sectional observations, logistic regression and leave-one-out cross-validation identified donor-specific, CD154 + T-cytotoxic (Tc)-memory cells as best associated with rejection outcomes. In the longitudinal cohort, (1) the association between CD154 + Tc-memory cells and rejection outcomes was replicated with sensitivity/specificity 92.3%/84.6% for observations at 1-60 days, and (2) elevated pre-LTx CD154 + Tc-memory cell responses were associated with significantly increased incidence (p = 0.02) and hazard (HR = 7.355) of rejection in survival/proportional hazard analysis. CD154 expression correlated with proliferative alloresponses (r = 0.835, p = 7.1e-07), and inversely with CTLA4 expression of allospecific CD154 + Tc-memory cells (r =-0.706, p = 3.0e-05). Allospecific CD154 + T-helper-memory cells, not CD154 + Tc-memory, were inhibited by increasing Tacrolimus concentrations (p = 0.026). Collectively, allospecific CD154 + T cells provide an estimate of rejection risk in children with LTx.

Wound healing activity of methanolic extract of leaves of Alternanthera brasiliana Kuntz using in vivo and in vitro model.

Wound healing activity of methanolic extract of leaves of Alternanthera brasiliana Kuntz was studied by excision and incision wound model (in vivo) in Sprague Dawley rats and by Chorioallantoic membrane (CAM) model (In vitro) in 9-day-old embryonated chicken eggs. In excision wound model, compared to the control group, per cent contraction of wound was significantly higher in A. brasiliana (5% w/w ointment) treated group. In incision wound model, tensile strength of the healing tissue after treatment with A. brasiliana was found to be significantly higher compared to the control group indicating better wound healing activity of the test plant. These findings were also confirmed by histopathological examination. The extract also promoted angiogenesis as evidenced by CAM model. The results suggested that methanolic extract of A. brasiliana possess significant wound healing potential in normal wound.

Pyrexia of unknown origin with neutropenia, cervical lymphadenopathy, pneumonia and marrow hypoplasia.

A 56 years adult male presented with fever for 3 weeks with neutropenia and cervical lymphadenopathy with left sided pneumonitis. Histopathology of lymphnode was consistent with Kikuchi's Necrotizing Lymphadenitis. Kikuchi's disease is usually a self- limiting illness characterized by pyrexia, neutropenia and cervical lymphadenopathy in young women of Asian decent. This often leads to the misdiagnosis of lymphoma or tuberculosis. The notable feature here is an older male presented with severe neutropenia and pneumonia with hypoplastic marrow.

Philadelphia chromosome positive essential thrombocythemia with dilated cardiomyopathy.

We report here an unusual case of a 30-year old male patient with essential thrombocythemia (ET) and dilated cardiomyopathy, who on further investigation was found to have Philadelphia chromosome positive (Ph+) cells in the bone marrow. The reverse transcriptase-polymerase chain reaction (RT-PCR) test on his peripheral blood leucocytes revealed b2a2 transcript of the bcr-abl fusion gene. Literature shows that the boundary line between Ph+ essential thrombocythemia and chronic myeloid leukemia (CML) is getting blurred day by day. Each one may be a part of the spectrum of a single clonal proliferative disease. Association of dilated cardiomyopathy with ET has not been reported.

Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

Contribution of efflux pumps in fluroquinolone resistance in multi-drug resistant nosocomial isolates of Pseudomanas aeruginosa from a tertiary referral hospital in north east India.

BACKGROUND: Pseudomonas aeruginosa is one of the leading opportunistic pathogen and its ability to acquire resistance against series of antimicrobial agents confine treatment option for nosocomial infections. Increasing resistance to fluroquinolone (FQ) agents has further worsened the scenario. The major mechanism of resistance to FQs includes mutation in FQs target genes in bacteria (DNA gyrase and/or topoisomerases) and overexpression of antibiotic efflux pumps. OBJECTIVE: We have investigated the role of efflux pump mediated FQ resistance in nosocomial isolates of P. aeruginosa from a tertiary referral hospital in north eastern part of India. MATERIALS AND METHODS: A total of 234 non-duplicate, consecutive clinical isolates of P. aeruginosa were obtained from a tertiary referral hospital of north-east India. An efflux pump inhibitor (EPI), carbonyl cyanide m-chlorophenylhydrazone (CCCP) based method was used for determination of efflux pump activity and multiplex polymerase chain reaction (PCR) was performed for molecular characterisation of efflux pump. Minimum inhibitory concentration (MIC) reduction assay was also performed for all the isolates. RESULTS AND CONCLUSION: A total number of 56 (23%) have shown efflux mediated FQ resistance. MexAB-OprM efflux system was predominant type. This is the first report of efflux pump mediated FQ resistance from this part of the world and the continued emergence of these mutants with such high MIC range from this part of the world demands serious awareness, diagnostic intervention, and proper therapeutic option.

An isoflavone from Myristica malabarica.

Phytochemical investigation of the heartwood of Myristica malabarica has led to the isolation of the new 7,4'-dimethoxy-5-hydroxyisoflavone together with two other isoflavones, biochanin A and prunetin, and a 1,3-diarylpropanol and a rare alpha-hydroxydihydrochalcone.

Modeling and optimization of rotational C-arm stereoscopic X-ray angiography.

Stereoscopy can be an effective method for obtaining three-dimensional (3-D) spatial information from two-dimensional (2-D) projection X-ray images, without the need for tomographic reconstruction. This much-needed information is missed in many X-ray diagnostic and interventional procedures, such as the treatment of vascular aneurysms. Fast C-arm X-ray systems can obtain multiple angle sequences of stereoscopic image pairs from a single contrast injection and a single breath hold. To advance this solution, we developed a model of stereo angiography, performed perception experiments and related results to optimal acquisition. The model described horizontal disparity for the C-arm geometry that agreed very well with measurements from a geometric phantom. The perceptual accommodation-convergence conflict and geometry limited the effective stereoscopic field of view (SFOV). For a typical large image intensifier system, it was 28 cm x 31 cm at the center of rotation (COR). In the model, blurring from finite focal-spot size and C-arm motion reduced depth resolution on the digital display. Near the COR, the predicted depth resolution was 3-11 mm for a viewing angle of 7 degrees , which agreed favorably with results from recently published studies. The model also described how acquisition parameters affected spatial warping of curves of equal apparent depth. Pincushioning and the difference between the acquisition and display geometry were found to introduce additional distortions to stereo displays. Preference studies on X-ray angiograms indicated that the ideal viewing angle should be small (1-2 degrees), which agreed with some previously published work. Perceptual studies indicated that stereo angiograms should have high artery contrast and that digital processing to increase contrast improved stereopsis. Digital subtraction angiograms, with different motion errors between the left and right-eye views, gave artifacts that confused stereopsis. The addition of background to subtracted images reduced this effect and provided other features for improved depth perception. Using the modeling results and typical clinical angiography requirements, we recommend acquisition protocols and engineering specifications that are achievable on current high-end systems.

Effect of various alkyl and unsaturated substituents on the mutagenicity of some nitrophenyl thioethers.

A variety of nitro-substituted phenyl alkyl/aryl thioethers and nitroso-substituted phenyl alkyl/aryl thioethers have been synthesized and tested for their mutagenicity towards Salmonella typhimurium strain TA100, TA98, TA98NR and TA98/1,8-DNP(6) in the absence of S9 mix. The relative order of mutagenicity in TA98 and TA100 among p-nitrophenyl thioethers having alkyl or aryl substituents is allyl>phenyl>benzyl>butyl>propyl>ethyl>methyl. Compounds having an alkyl chain C(6) to C(12) were found to be non-mutagenic. Among the various positional isomers (ortho, meta and para) of nitro-substituted diphenyl thioethers only the compounds having the -NO(2) function at the para position is mutagenic, whereas compounds having a -NO(2) function at ortho and meta are non-mutagenic. However, the reduced intermediate, ortho-nitroso derivative was found to be mutagenic in all the four strains but the meta-nitroso derivative was found to be non-mutagenic. All mutagens were found to be non-mutagenic when tested in nitroreductase deficient strain TA98NR, whereas their nitroso intermediates are found to be mutagenic. A substantial fall in the mutagenic activity is observed when some mutagens are tested in O-acetyltransferase deficient strain TA98/1,8-DNP(6).

Factors associated with HIV infection among Indian women.

There is still a paucity of research on the sociodemographic and other underlying factors associated with HIV transmission among women in India. This study was designed to investigate such factors in sexually experienced Indian women. We used data from the National Family Health Survey 3 (NFHS-3), which tested 52,853 women for HIV, including 27,556 husband and wife pairs. Significant risk factors for all women and married women only were: aged 26-35 years (adjusted odds ratios [AORs] = 3.65 and 2.53, respectively), being poor (AORs = 1.57 and 1.79), having had a genital sore in the last 12 months (AORs = 3.16 and 3.01) and having more than one sexual partner (AORs = 5.95 and 5.15). For husband and wife pairs, suffering sexual violence (AOR = 2.63), husband having other wife/wives (AOR = 3.40) and husband's education being secondary level or higher (AOR = 0.43) were significant. Intervention strategies in India should target young married (aged 25-35 years) and formerly married urban women who are poor, as well as those who have suffered sexual violence from their husbands, and/or are (or whose husbands are) multi-partnered. Empowerment of women is fundamental to HIV/AIDS prevention in India.

Evaluation of binding property of mucilage from Litsea glutinosa wall.

BACKGROUND: Litsea glitinosa is an evergreen tree of medium size which grows to a height of about 20 to 30 feet. It belongs to family Lauraceae. In India it is found mainly in North Eastern region. The leaves and the mucilage from the bark of plant is utilized in the gum for poultices. METHODS: Mucilage of Litsea glutinosa was isolated from powdered bark by continuous hot extraction technique using water and precipitation by absolute alcohol (38% w/w yield). The mucilage was evaluated for binding properties in tablets and granules, using paracetamol as a model drug. The granules were prepared using 4 different concentrations of mucilage (4%, 6%, 8%, and 10%) and evaluated for percentage of fines, average particle size, total porosity, compressibility index, and flow properties. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time, and in vitro dissolution profiles. RESULTS: The results obtained with the lower concentrations of mucilage, that is, less than 6% were not so encouraging. The tablets prepared by using 10% mucilage of L. glutinosa as binder exhibited more hardness as compared with the starch. CONCLUSION: It may be concluded that the concentration ranging from 6% to 8% of L. glutinosa mucilage may be considered as better option as a binding agent for the preparation of tablets as compared to the starch (10%).