Expert panel recommendations for topical hemostatic agent use in varied bleeding sites and situations during neuro-spine surgeries.

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.

The DNA damage response in advanced ovarian cancer: functional analysis combined with machine learning identifies signatures that correlate with chemotherapy sensitivity and patient outcome.

BACKGROUND: Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant. Comprising five pathways, DDR redundancy is complex and rarely studied alongside chemoresistance influence from mitochondrial dysfunction. We developed functional assays to monitor DDR and mitochondrial states and trialled this suite on patient explants. METHODS: We profiled DDR and mitochondrial signatures in cultures from 16 primary-setting ovarian cancer patients receiving platinum chemotherapy. Explant signature relationships to patient progression-free (PFS) and overall survival (OS) were assessed by multiple statistical and machine-learning methods. RESULTS: DR dysregulation was wide-ranging. Defective HR (HRD) and NHEJ were near-mutually exclusive. HRD patients (44%) had increased SSB abrogation. HR competence was associated with perturbed mitochondria (78% vs 57% HRD) while every relapse patient harboured dysfunctional mitochondria. DDR signatures classified explant platinum cytotoxicity and mitochondrial dysregulation. Importantly, explant signatures classified patient PFS and OS. CONCLUSIONS: Whilst individual pathway scores are mechanistically insufficient to describe resistance, holistic DDR and mitochondrial states accurately predict patient survival. Our assay suite demonstrates promise for translational chemosensitivity prediction.

Cryoprotection of humanin-like peptides in seminal plasma for ejaculated spermatozoa of crossbred bulls.

BACKGROUND: Cryopreservation process negatively affects spermatozoa functions. Humanin, a small polypeptide encoded in the mitochondrial genome, is well known for its role in cell survival. OBJECTIVE: To quantify the endogenous levels of humanin in seminal plasma of crossbred Frieswal bulls and to study its role in cryoprotection. The presence of humanin in bull spermatozoa was also investigated. MATERIALS AND METHODS: A total of 40 semen samples were separated into two groups based on the initial progressive motility (IPM): Good (IPM >70%) and Poor (IPM <50%) groups; and/or based on the post-thaw motility (PTM): Freezable (PTM>50%) and Non-freezable (PTM < 50%) groups. Humanin concentration in seminal plasma (SP-HN) was quantified using ELISA. RESULTS: SP-HN concentration ranged from undetectable to 67.6 pg/mL with a median level of 35.2 pg/mL. SP-HN level was significantly higher in the good quality semen group than in the poor quality semen group (p<0.001), and also significantly higher in the freezable group than in the non-freezable group (p<0.001). SP-HN level was positively correlated with initial progressive motility, post-thaw semen motility, viability, acrosome intactness and plasma membrane integrity, but negatively correlated the level of reactive oxygen species and malondialdehyde content. Immunochemical localization showed the presence of humanin in the proximal region of the middle piece of spermatozoa. CONCLUSION: Endogenous humanin level had significant correlation with semen quality and might protect sperm cells against freeze-induced oxidative stress. doi.org/10.54680/fr22510110712.

Ethylenediamine mediated luminescence enhancement of pollutant derivatized carbon quantum dots for intracellular trinitrotoluene detection: soot to shine.

Vehicle-generated toxic pollutants are composed of gaseous smoke and particulate byproducts accumulated as a black substance at its exhaust. This particulate matter (soot) is utilized for the green synthesis of highly stable, non-toxic, environment friendly, carbon quantum dots (CQD). The CQDs are synthesized via the simple hydrothermal route in the absence (C1) and presence (C2) of oxidants. The as-synthesized CQDs are amine functionalized using ethylenediamine. The amine functionalized CQDs (C1N and C2N) are explored for trinitrotoluene detection. From transmission electron microscopy, the average size of C1 and C2 was found to be about 4.2 nm and 5.6 nm respectively. The incorporation of amine groups lead to an increase in quantum yields from 5.63% to 12.7% for C1 and from 3.25% to 8.48% for C2 QDs. A limit of detection (LOD) of 13 ppb was displayed by C1N while the LODs of 11 ppb and 4.97 ppb were delivered by C2N at λ ex 370 nm and λ ex 420 nm respectively. The Stern-Volmer constant for C1N is 2.02 × 106 M-1 while for C2N at λ ex 370 nm and λ ex 420 nm is 0.38 × 106 M-1 and 0.48 × 106 M-1 respectively. Furthermore, C1N presents high selectivity for TNT compared to C2N. Owing to their higher luminescence, C1N particles are successfully demonstrated for their applicability in intracellular TNT detection.

Higher rate of central nervous system involvement by flow cytometry than morphology in acute lymphoblastic leukemia.

INTRODUCTION: Central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is diagnosed traditionally by cytopathology (CP) of the cerebrospinal fluid (CSF). Role of flow cytometry (FC) to diagnose CNS involvement has not been extensively investigated. METHODS: We aimed to detect CNS involvement in 42 ALL patients (33 B-ALL, nine T-ALL) at diagnosis by FC and comparing it with CP and to correlate it with known risk factors for CNS disease like Lactate dehydrogenase (LDH). A receiver operating characteristic curve was used to determine the cutoff of LDH to predict CSF involvement. For the analysis of categorical/quantitative variables, Fisher's exact test was used. For the analysis of continuous variables, Mann-Whitney test was used. A P value of <.05 was taken as significant. RESULTS: CP and FC were positive in five (11.9%) and 11 patients (26.14%) respectively with FC detecting a significantly higher level of involvement (P=.001). All CP-positive cases were FC positive. A LDH value of >472 U/L had a sensitivity of 61% and specificity of 62.5% for diagnosis of CSF involvement by FC. CONCLUSIONS: CSF FC detects CNS disease in ALL patients at diagnosis at a rate double than CP alone and is statistically associated with an elevated LDH level. It should be incorporated in the evaluation of CSF to detect CNS involvement.

Optimization of food materials for development of nutritious pasta utilizing groundnut meal and beetroot.

Present study was undertaken to optimize the level of food materials viz. groundnut meal, beetroot juice and refined wheat flour for development of nutritious pasta using response surface methodology. Box-benken design of experiments was used to design different experimental combinations considering 10 to 20 g groundnut meal, 6 to 18 mL beetroot juice and 80 to 90 g refined wheat flour. Quality attributes such as protein content, antioxidant activity, colour, cooking quality (solid loss, rehydration ratio and cooking time) and sensory acceptability of pasta samples were the dependent variables for the study. The results revealed that pasta samples with higher levels of groundnut meal and beetroot juice were high in antioxidant activity and overall sensory acceptability. The samples with higher content of groundnut meal indicated higher protein contents in them. On the other hand, the samples with higher beetroot juice content were high in rehydration ratio and lesser cooking time along with low solid loss in cooking water. The different level of studied food materials significantly affected the colour quality of pasta samples. Optimized combination for development of nutritious pasta consisted of 20 g groundnut meal, 18 mL beetroot juice and 83.49 g refined wheat flour with overall desirability as 0.905. This pasta sample required 5.5 min to cook and showed 1.37 % solid loss and rehydration ratio as 6.28. Pasta sample prepared following optimized formulation provided 19.56 % protein content, 23.95 % antioxidant activity and 125.89 mg/100 g total phenols with overall sensory acceptability scores 8.71.

Epidemiology, Clinico-Haematological Profile and Management of Aplastic Anaemia: AIIMS Experience.

BACKGROUND: The incidence of aplastic anaemia (AA) is higher in Asia than in the West. The precise incidence of AA in India is not known due to lack of epidemiological study. 20-40% of pancytopenic patients in referral centres are of aplastic anaemia. PATIENTS AND METHODS: This was an analysis of 1501 patients diagnosed with aplastic anaemia over a period of seven and half years (January 2007- June 2014) attending the Aplastic clinic of department of haematology of All India Institute of Medical Sciences, New Delhi. The details regarding medical history, physical examination, complete blood count, bone marrow aspirate and biopsy, treatment received, were retrieved. Inherited bone marrow failure was screened in patients below 35 years. Treatment response was analysed for various treatment modalities. RESULTS: 1501 patients of AA from 20 different states of India were analysed. The bulk of patients were from Uttar Pradesh (28.7%), Bihar (23.6%), Delhi/NCR (20%) and Haryana (7%).The average number of new aplastic anaemia patients enrolled per year 214 (range: 101 -263). The median age at presentation was 25 years (range 2-83),with M;F - 2.3:1. Severity of AA revealed: severe (SAA): 75%, very severe (VSAA): 15%, non-severe (NSAA): 10%. Inherited bone marrow failure syndromes constituted 5% (75 patients) of all aplastic anaemia patients. The most common clinical presentations were pallor (97%), bleeding manifestations (69.6%) and fever (54%). The haematological parameters showed: median level of haemoglobin level: 5.9 gm/dL, WBC: 2700/mm3, ANC: 380/mm3, platelet: 1 0000/mm3. PNH clone was present in 13.5% of patients. 107 patients (7%) were lost to follow up or expired before any treatment was initiated. Only 69 patients (4.5%) received treatment with HLA-matched sibling stem cell transplantation and another 232 (15.5%) patients received ATG plus cyclosporine as immunosuppressive therapy. Seven hundred thirteenpatients (47.5%) received cyclosporine. The overall response to various treatment modalities was: HLA matched sibling haematopoietic stem cell transplant: 75.3%, Anti-thymocyte globulin plus cyclosporine: 58.7%, cyclosporine plus androgen: 45.6%, cyclosporine alone: 32.2%. CONCLUSION: Management of AA is a real challenge in developing countries.This is one of the largest case series from a single centre from India. It is our endeavour to reduce the detrimental outcome by increasing awareness among patients and referring physicians to reduce the delay between diagnosis and treatment.

Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review.

Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease.

NSE/αNAE positivity in B-lineage acute lymphoblastic leukemia: revisiting a potential cytochemical diagnostic pitfall.

Cytochemical staining for leukemia typing is declining in hematology laboratories, but the use of flow cytometry may not be possible in some settings. Aberrant cytochemical nonspecific esterase/α-naphthyl acetate esterase (NSE/αNAE) positive B-lymphoblasts can cause confusion with monoblasts, a potentially dangerous pitfall. This unusual cytochemical NSE/αNAE positivity had been associated with relatively poorer outcome of acute lymphoblastic leukemia (ALL) in the era prior to the advent of routine multicolor flow cytometric immunophenotyping. We reviewed morphological, cytochemical and flow-cytometric data from five cases of B-lineage ALL that showed NSE/αNAE positivity and were diagnosed definitively using multi-parametric flow cytometric immunophenotypic analysis. Diffuse or dot-like (localized) strong cytochemical NSE/αNAE activity was detected in all cases and all showed one or more features of high risk disease. The number of NSE/αNAE positive blasts in the marrow varied from 10 to 75%. The morphological differential diagnoses included T-lymphoid lineage ALL and acute monoblastic leukemia (AML-M5). Flow cytometric data revealed B-lineage antigens and the absence of monocytic or other myeloid markers resolved the diagnosis. These cases underscore the importance of immunophenotyping in all cases of suspected ALL regardless of the cytochemical findings. Although the numbers are small, the association with high risk disease observed in all five of our cases may corroborate the previously reported poor prognostic value of such aberrant cytochemical staining.

Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice.

High levels of homocysteine (Hcy), known as hyperhomocysteinemia are associated with neurovascular diseases. H2S, a metabolite of Hcy, has potent anti-oxidant and anti-inflammatory activities; however, the effect of H2S has not been explored in Hcy (IC)-induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy-induced neurodegeneration and neurovascular dysfunction. To test this hypothesis we employed wild-type (WT) males ages 8-10 weeks, WT+artificial cerebrospinal fluid (aCSF), WT+Hcy (0.5 µmol/µl) intracerebral injection (IC, one time only prior to NaHS treatment), WT+Hcy+NaHS (sodium hydrogen sulfide, precursor of H2S, 30 µmol/kg, body weight). NaHS was injected i.p. once daily for the period of 7 days after the Hcy (IC) injection. Hcy treatment significantly increased malondialdehyde, nitrite level, acetylcholinestrase activity, tumor necrosis factor-alpha, interleukin-1 beta, glial fibrillary acidic protein, inducible nitric oxide synthase, endothelial nitric oxide synthase and decreased glutathione level indicating oxidative-nitrosative stress and neuroinflammation as compared to control and aCSF-treated groups. Further, increased expression of neuron-specific enolase, S100B and decreased expression of (post-synaptic density-95, synaptosome-associated protein-97) synaptic protein indicated neurodegeneration. Brain sections of Hcy-treated mice showed damage in the cortical area and periventricular cells. Terminal deoxynucleotidyl transferase-mediated, dUTP nick-end labeling-positive cells and Fluro Jade-C staining indicated apoptosis and neurodegeneration. The increased expression of matrix metalloproteinase (MMP) MMP9, MMP2 and decreased expression of tissue inhibitor of metalloproteinase (TIMP) TIMP-1, TIMP-2, tight junction proteins (zonula occulden 1) in Hcy-treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy-induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.

Efficacy of Seabuckthorn (Hippophae rhamnoides) Oil vis-a-vis Other Standard Drugs for Management of Gastric Ulceration and Erosions in Dogs.

The study was conducted on 20 adult healthy medium-sized mongrel dogs. Injection of dexamethasone @ 1 mg/kg, IV, b.i.d., was administered to create gastric ulcerations and erosions. Thereafter all the animals were randomly divided into 5 equal treatment groups. Animals of groups I, II, III, IV, and V were treated with oral administration of lansoprazole @ 1.5 mg/kg, sucralfate @ 1 g/animal, misoprostol @ 10 µg/kg, famotidine @ 1 mg/kg, and Seabuckthorn seed oil @ 5 mL/animal, twice a day, respectively. Gastroendoscopically, complete healing of GUE lesions was earliest in Seabuckthorn- (SBT-) oil-treated group (7.5 ± 0.87) followed by famotidine (8.25 ± 1.44), lansoprazole (9.00 ± 1.23), misoprostol (10.50 ± 1.50), and sucralfate (13.50 ± 0.87), respectively. A marked improvement in appetite was observed in all animals. Melena was continued till day 3 in SBT group, day 6 in lansoprazole- and famotidine-treated animals, and day 9 in sucralfate and misoprostol group animals. Fecal occult blood test was positive in all animals till there was endoscopic evidence of gastric bleeding. Hematological parameters improved markedly towards the end of the study. Serum biochemical parameters remained within normal physiological limits throughout the study. It is concluded that Seabuckthorn oil was the best therapeutic agent for dexamethasone-induced GUE in dogs followed by famotidine, lansoprazole, misoprostol, and sucralfate.

TIMP-2 mutant decreases MMP-2 activity and augments pressure overload induced LV dysfunction and heart failure.

Pressure overload induces cardiac extracellular matrix (ECM) remodelling and results in heart failure. ECM remodelling by matrix metalloproteinases (MMPs) is primarily regulated by their target inhibitors, tissue inhibitor of matrix metalloproteinases (TIMPs). It is known that TIMP-2 is highly expressed in myocardium and is required for cell surface activation of pro-MMP-2. We and others have reported that imbalance between angiogenic growth factors and anti-angiogenic factors results in transition from compensatory cardiac hypertrophy to heart failure. We previously reported the pro-angiogenic role of MMP-2 in cardiac compensation, however, the specific role of TIMP-2 during pressure overload is yet unclear. We hypothesize that genetic ablation of TIMP-2 exacerbates the adverse cardiac matrix remodelling due to lack of pro-angiogenic MMP-2 and increase in anti-angiogenic factors during pressure overload stress and results in severe heart failure. To verify this, ascending aortic banding (AB) was created to mimic pressure overload, in wild type C57BL6/J and TIMP-2-/- (model of MMP-2 deficiency) mice. Left ventricular (LV) function assessed by echocardiography and pressure-volume loop studies showed severe LV dysfunction in TIMP-2-/- AB mice compared to controls. Expression of MMP-2, vascular endothelial growth factor (VEGF) was decreased and expression of MMP-9, anti-angiogenic factors endostatin and angiostatin was increased in TIMP-2-/- AB mice compared with wild type AB mice. Connexins (Cx) are the gap junction proteins that are widely present in the myocardium and play an important role in endothelial-myocyte coupling. Our results showed that expression of Cx 37 and 43 was decreased in TIMP-2-/- AB mice compared with corresponding wild type controls. These results suggest that genetic ablation of TIMP-2 decrease the expression of pro-angiogenic MMP-2, VEGF and increases anti-angiogenic factors that results in exacerbated abnormal ventricular remodelling leading to severe heart failure.

Hyperhomocysteinemia decreases intestinal motility leading to constipation.

Elevated levels of plasma homocysteine (Hcy) called hyperhomocysteinemia (HHcy) have been implicated in inflammation and remodeling in intestinal vasculature, and HHcy is also known to aggravate the pathogenesis of inflammatory bowel disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels in the plasma. We hypothesize that HHcy decreases intestinal motility through matrix metalloproteinase-9 (MMP-9)-induced intestinal remodeling leading to constipation. To verify this hypothesis, we used C57BL/6J or wild-type (WT), cystathionine ß-synthase (CBS(+/-)), MMP-9(-/-), and MMP-9(-/-) + Hcy mice. Intestinal motility was assessed by barium meal studies and daily feces output. Plasma Hcy levels were measured by HPLC. Expression of ICAM-1, inducible nitric oxide synthase, MMP-9, and tissue inhibitors of MMPs was studied by Western blot and immunohistochemistry. Reactive oxygen species (ROS) including super oxide were measured by the Invitrogen molecular probe method. Tissue nitric oxide levels were assessed by a commercially available kit. Plasma Hcy levels in the treated MMP-9 group mice were comparable to CBS(+/-) mice. Barium meal studies suggest that intestinal motility is significantly decreased in CBS(+/-) mice compared with other groups. Fecal output-to-body weight ratio was significantly reduced in CBS(+/-) mice compared with other groups. There was significant upregulation of MMP-9, iNOS, and ICAM-1 expression in the colon from CBS(+/-) mice compared with WT mice. Levels of ROS, superoxide, and inducible nitric oxide were elevated in the CBS(+/-) mice compared with other groups. Results suggest that HHcy decreases intestinal motility due to MMP-9-induced intestinal remodeling leading to constipation.

X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice.

Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS-/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2-/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS-/+ (HHcy), MMP-9-/-, PAR-1-/+ and Ins2-/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS-/+ and Akita hearts decreased while it was increased in lungs of CBS-/+ and MMP-9-/-.There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS-/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

Heart rate variability assessment to stratify risk of autonomic imbalance during subarachnoid block: A prospective study.

BACKGROUND: Hypotension after subarachnoid block is a common adverse event which can be predicted by simple, safe and indirect measure of autonomic activity. CONTEXT: Heart rate variability has been accepted as an indirect measure of autonomic activity. AIM: It was to evaluate preoperatively risk of hypotension after subarachnoid block. SETTING AND DESIGN: This is controlled, randomized blind prospective study. MATERIALS AND METHODS: One hundred adult patients of either sex in the age group of 25 to 60 years belonging to ASA physical status of I to III, scheduled for elective infra-umbilical surgery, were enrolled for this randomized prospective study. During preanesthetic check their HRV was analyzed for time domain and frequency domain parameters. They were classified into two groups of 50 patients each depending on their low to high frequency ratios (LF/HF). Group I included patients with LF/HF <2.5 and Group II included patients with LF/HF >2.5. Sensitivity of LF/HF for prediction of hypotension greater than 20% of baseline was tested. RESULT: The present study showed significant differences of systolic blood pressure (SBP) after subarachnoid block, depending on baseline LF/HF. Patients with low LF/HF showed lowest SBP of 106.08 ± 3.19 (15.22% fall of base line SBP) as compared to high LF/HF which showed 87.62 ± 8.71 (30.26% fall of base line SBP). Baseline LF/HF parameter correlated significantly with proportionate decrease in SBP after subarachnoid blocks. STATISTICAL ANALYSIS: Hemodynamic parameter was analyzed by using student t test on statgraphic version 5.1. CONCLUSION: Analysis of low and high frequency ratio, reflect autonomic control and may be used as an indirect measure for risk stratification of hypotension after subarachnoid block with high sensitivity.

Mesenteric vascular remodeling in hyperhomocysteinemia.

Remodeling by its very nature implies synthesis and degradation of extracellular matrix components (such as elastin, collagen, and connexins). Most of the vascular matrix metalloproteinase (MMP) are latent because of the presence of constitutive nitric oxide (NO). However, during oxidative stress peroxinitrite (ONOO-) activates the latent MMPs and instigates vascular remodeling. Interestingly, in mesenteric artery, homocysteine (Hcy) decreases the NO bio-availability, and folic acid (FA, an Hcy-lowering agent) mitigates the Hcy-mediated mesentery artery dysfunction. Dimethylarginine dimethylaminohydrolase-2 (DDAH-2) and endothelial nitric oxide synthase (eNOS) increases NO production. The hypothesis was that the Hcy decreased NO bio-availability, in part, activating MMP, decreasing elastin, DDAH-2, eNOS and increased vasomotor response by increasing connexin. To test this hypothesis,the authors used 12-week-old C57BJ/L6 wild type (WT) and hyperhomocysteinemic (HHcy)-cystathione beta synthase heterozygote knockout (CBS+/-) mice. Blood pressure measurements were made by radio-telemetry. WT and MMP-9 knockout mice were administered with Hcy (0.67 mg/ml in drinking water). Superior mesenteric artery and mesenteric arcade were analyzed with light and confocal microscopy. The protein expressions were measured by western blot analysis. The mRNA levels for MMP-9 were measured by RT-PCR. The data showed decreased DDAH-2 and eNOS expressions in mesentery in CBS-/+ mice compared with WT mice. Immuno-fluorescence and western blot results suggest increased MMP-9 and connexin-40 expression in mesenteric arcades of CBS-/+ mice compared with WT mice. The wall thickness of third-order mesenteric artery was increased in CBS-/+ mice compared to WT mice. Hcy treatment increased blood pressure in WT mice. Interestingly, in MMP-9 KO, Hcy did not increase blood pressure. These results may suggest that HHcy causes mesenteric artery remodeling and narrowing by activating MMP-9 and decreasing DDAH-2 and eNOS expressions, compromising the blood flow, instigating hypertension, and acute abdomen pain.

Smile Train project: a blessing for population of lower socio-economic status.

The Smile Train Project is an international charity dedicated to poor children with cleft lip and cleft palate abnormalities with an aim to restore normal or near normal anatomy, function, satisfactory facial appearance and speech. A review was done among 241 patients of cleft lip and palate anomaly, admitted at Subharti Medical College, Meerut, for cheiloplasty and palatoplasty between May 2006 and December 2008 in collaboration with the department of maxillofacial surgery and its incidence in relation to age and sex distribution. Ideally infants with cleft lip alone should be repaired within the first six months of age and cleft palate should be repaired before development of speech ie, at the age of 2 years. But in this study only 25% of patients who underwent corrective surgery were up to 2 years of age and more than 47% cases were operated between the ages of 2 and 10 years. Sixty-six cases (27%) were operated between ages of 10 and 35 years. It may be due to ignorance, poverty or unawareness about the fact that cleft anomaly can be corrected by surgery. Without repair, these children would have suffered from facial disfigurement, feeding problems, social isolation and abnormal speech. Smile Train Project along with motivation of health workers of this institute has made their smiles more socially acceptable.

Anesthetic management for Smile Train a blessing for population of low socioeconomic status: A prospective study.

BACKGROUND: The Smile Train is an international charity with an aim to restore satisfactory facial appearance and speech for poor children with cleft abnormalities who would not otherwise be helped. A total of 241 children of cleft lip and palate anomaly, scheduled for surgery under general anesthesia, were studied. Cleft abnormality requires early surgery. Ideally cleft lip in infants should be repaired within the first 6 months of age; and cleft palate, before development of speech, i.e., at the age of 2 years. But in our study, only 27% of children underwent corrective surgery by ideal age of 2 years, which may be due to ignorance, poverty or unawareness about the fact that cleft anomaly can be corrected by surgery. CONTEXT: Smile Train provides care for poor children with clefts in developing countries. The guidelines were designed to promote safe general anesthesia for cheiloplasty and palatoplasty. AIMS: Smile Train promotes free surgery for cleft abnormalities to restore satisfactory facial appearance and speech. SETTINGS AND DESIGN: This was a randomized prospective cohort observational study. MATERIALS AND METHODS: A total of 241 consenting patients of American Society of Anesthesiologt (ASA) I and II aged 6 months to 20 years of either sex, scheduled for elective cheiloplasty and palatoplasty, were studied. Children suffering from anemia, fever, upper respiratory tract infections or any associated congenital anomalies were excluded. Approved guidelines of the Smile Train Medical Advisory Board were observed for general anesthesia and surgery. STATISTICAL ANALYSIS: The Student t test was used. RESULTS: The infants were anemic and undernourished, and two thirds of the children were male. Only 27% of the children presented for surgery by the ideal age of 2 years. CONCLUSIONS: Pediatric anesthesia carries a high risk due to congenital anomaly and shared airway, venous access and resuscitation; however, cleft abnormality requires surgery at an early age to make the smiles of affected children more socially acceptable.