Switch the click: Ultrafast photochemistry of photoDIBO-OH tracked by time-resolved IR spectroscopy.

Click chemistry refers to selective reactions developed for grafting of bio(macro)molecules in their biological media. Caged click compounds have been employed to spatiotemporally control click reactions. Here, we survey the uncaging of photo-dibenzocyclooctyne-OH (photoDIBO-OH) to its click-chemistry active form DIBO-OH, with particular attention to its conversion timescale and efficiency. Ultraviolet pump-infrared probe experiments reveal a stepwise decarbonylation: first, carbon monoxide (C≡O) is released within 1.8 ps, and then, it converts, within 10 ps, to DIBO-OH. Completion of uncaging is achieved with an efficiency of ∼50%. A successful demonstration of two-photon uncaging of photoDIBO-OH at long wavelength (700 nm) confers enhanced in vivo compatibility and proceeds on the same timescale.

Behavioural incongruities in juvenile Cyprinus carpio exposed to organophosphate compounds.

For the ever increasing human population, the necessity to produce the food in large quantities has become the main goal internationally which has led to increase the practice of pesticides globally. Presence of pesticides in aquatic water bodies is largely due to the runoff from agricultural fields causing to deteriorate the healthy characteristics of an aquatic environment system leading to the toxic impact on non-target aquatic organism such as fish. Approach: In fish, there are various portal of entry through which the contaminants enter. Via various routes, the contaminants reach into the blood and subsequently to different organs or systems. Since Pesticides are known to modify the behavior of animals when exposed to toxic levels. The behavioral changes may be caused by the changes in the nervous system triggered directly or through metabolic or physiological activities. However, the effects have been found to be multifarious and known to differ at different concentrations. Also, Blood is the most accessible component of the vertebrate body fluid system and consequences of direct and indirect damage to blood cells and their precursors are predictable and potentially life threatening. Therefore, behavioural and genotoxicological studies have been considered and used as diagnostic tool in order to investigate behavioural and genotoxicological alterations. This study was undertaken to investigate behavioural changes in Cyprinus carpio exposed to two organophosphate compounds, chlorpyrifos (cpf) and dimethoate (dim). Fishes weighing 10 ± 2 g were exposed to sub-lethal concentrations of cpf (0.76 ppb, 1.52 ppb, 2.28 ppb, 3.04 ppb and 3.8 ppb) and dimethoate (0.22 ppm, 0.44 ppm, 0.66 ppm, 0.88 ppm and 1.1 ppm) for the period of 96 h and various behavioural indices were evaluated during that period. Both the pesticides were found to induce behavioral toxicity in fishes such as drop in swimming velocity, reduced swimming activity and retarded opercular movements. Cpf was found more detrimental as compared to dimethoate in all cases. Fishes also elicited a genotoxic response which was evaluated by calculating the frequency of micronuclei formation in their hematocytes after 21 days of exposure. Chlorpyrifos induced more genotoxicity than dimethoate which was found dose and time dependent. Conclusion: It was concluded that the behavioural and genotoxic alterations in common carp could be applied as possible biomarkers in risk assessment and monitoring programs for pesticide contamination of aquatic ecosystems. Contribution: This study is one of its kind and will help to form baseline data.

Conservative Lateral Approach for Pleomorphic Adenomas of Parotid Gland Involving the Parapharyngeal Space-A Case Series.

The aim of this paper is to present and discuss the symptoms, clinical signs, diagnostic methods and a conservative surgical approach to large parotid pleomorphic adenomas arising from deep lobe and extending to the parapharyngeal space. In this case series we are describing four such cases which presented with painless swelling of different sizes in the parotid region along with intraoral swelling. Detailed diagnostic workup which included computed tomography scan, fine needle aspiration biopsy and magnetic resonance imaging was undretaken for confirming the diagnosis. Complete excision of the tumour via transcervical and transparotid approach without mandibulotomy and after securing local neurovascular structures was performed in all cases. This conservative lateral approach reduces the likelihood of complications. All the four patients were discharged without any complications and a proper follow up was done.

Dimethoate Induced Behavioural Changes in Juveniles of Cyprinus carpio var. communis under Temperate Conditions of Kashmir, India.

The present study was designed to investigate acute toxicity of dimethoate on juvenile Cyprinus carpio var. communis. Fishes weighing 10 ± 2 gms were selected and mortality data was statistically evaluated by Finney's Probit Method. The 96-hour LC50 value for Cyprinus carpio was found as 1.1 ppm in static bioassay system. Mean values of physicochemical parameters of aquarium waters determined during bioassay depicted slight variation indicating that the mortality in aquarium fishes occurred due to pesticide exposure and not suffocation. Lab. temperature ranged from 12 to 13°C; water temperature ranged from 11 to 12°C; dissolved oxygen ranged from 3.90 to 4.56 mg/L; pH ranged from 6.90 to 7.05; total dissolved solids ranged from 2.66 to 3.0 × 10(3) mg/L, while CO2 remained at a constant value of 2.0 mg/L. The fishes elicited various behavioural responses such as uncoordinated movements, convulsions, excessive mucus secretion, and imbalanced swimming which ended in a collapse to the bottom of the aquarium. Prior to death, the clinical signs like scale erosion, pale body colour, and hemorrhagic patches over the body were noticed which became more vivid up to the termination of experiments. Results of the study indicate potential toxicity of dimethoate in fingerlings of common carp for which the natural waterbodies must be continuously monitored to reduce its impact across food chains.

Comparative evaluation of genotoxicity by micronucleus assay in the buccal mucosa over comet assay in peripheral blood in oral precancer and cancer patients.

Early detection and quantification of DNA damage in oral premalignancy or malignancy may help in management of the disease and improve survival rates. The comet assay has been successfully utilised to detect DNA damage in oral premalignant or malignancy. However, due to the invasive nature of collecting blood, it may be painful for many unwilling patients. This study compares the micronucleus (MN) assay in oral buccal mucosa cells with the comet assay in peripheral blood cells in a subset of oral habit-induced precancer and cancer patients. For this, MN assay of exfoliated epithelial cells was compared with comet assay of peripheral blood leucocytes among 260 participants, including those with oral lichen planus (OLP; n = 52), leukoplakia (LPK; n = 51), oral submucous fibrosis (OSF; n = 51), oral squamous cell carcinoma (OSCC; n = 54) and normal volunteers (n = 52). Among the precancer groups, LPK patients showed significantly higher levels of DNA damage as reflected by both comet tail length (P < 0.0001) and micronuclei (MNi) frequency (P = 0.0009). The DNA damage pattern in precancer and cancer patients was OLP < OSF < LPK < OSCC, and with respective oral habits, it was multiple habits > cigarette + khaini > cigarette smokers > areca + khaini > areca. There was no significant difference in the comet length and MNi frequency between males and females who had oral chewing habits. An overall significant correlation was observed between MNi frequency and comet tail length with r = 0.844 and P < 0.0001. Thus, the extent of DNA damage evaluation by the comet assay in peripheral blood cells is perfectly reflected by the MN assay on oral exfoliated epithelial cells, and MNi frequency can be used with the same effectiveness and greater efficiency in early detection of oral premalignant conditions.

Pleomorphic adenoma of hard palate: an experience.

INTRODUCTION: Pleomorphic adenoma of minor salivary glands of hard palate is a rare benign tumour. It usually presents as slow growing submucosal mass on hard palate. The purpose of this study was to collect observational data regarding age, size, symptoms, CT findings and treatment of pleomorphic adenoma of hard palate. MATERIAL AND METHODS: The prospective observational study was done in the Department of ENT, Department of Oral and maxillofacial surgery at SKIMS Medical College and at Peoples Care Polyclinic for a period of 2 years. Twenty cases were enrolled in the study. After clinical suspicion, computed tomography, FNAC and core needle biopsy was done in all twenty cases before any surgical intervention was done. RESULTS: Most common age group seen to be involved was 16-30 years. Most common symptom was submucosal slow growing mass. Core biopsy was diagnostic with 100 % efficacy. On CT scan twelve patients (60 %) were seen to have intact hard palate even without minor erosions while four patients had full thickness erosion of hard palate. Surgical wide excision was done in all cases and one patient needed total maxillectomy. All treated patients were followed for one year and none showed signs of recurrence. CONCLUSION: Pleomorphic adenoma of hard palate is usually seen in adults. Definitive diagnosis lies on histopathological examination. CT is necessary for ruling out any bony erosion. Treatment is by wide local excision.

Clinical characteristics and comparative study of different modalities of treatment of pseudocyst pinna.

The aims of the article were to study the clinical characteristic of patients with pseudocysts and to compare different common modalities of treatment and introduce the concept of observation in pseudocyst management. Twenty-eight patients were diagnosed with pseudocyst of the auricle between June 2009 and June 2011 in a medical college hospital. The patients were divided into four groups each of seven patients on the basis of primary treatment offered. Four primary treatments offered were simple aspiration, aspiration with intralesional steroid, incision and drainage with removal of anterior cartilage leaflet with buttoning, and lastly, simple observation and reassurance. All 28 patients were male with involvement of right side more than left and no one had bilateral involvement. Adults in the age group of 30-40 were commonly affected. Most of the patients had history of significant trauma by security forces. Most common site of involvement was scaphoid and triangular fossa. The best form of treatment with minimum recurrence was incision and drainage with removal of anterior cartilage leaflet with buttoning. Simple observation as a treatment option was found to be as good as intralesional steroids. Pseudocyst of the pinna is a benign condition of unknown etiology affecting the pinna, commonly encountered in middle-aged men. It is a rare condition and is hardly encountered in routine ENT practice. Bilateral diseases are uncommon. Most common site of occurrence is triangular and scaphoid fossa. Many modalities of treatment have been recommended in literature with varied recurrence and failure rates. The best treatment is surgical deroofing followed by buttoning with minimum recurrences. An option of simple observation for 2-3 months should be discussed with each patient and was found to be as good as intralesional steroids.

Poor glycaemic control is the major factor associated with increased frequency of gastrointestinal symptoms in patients with diabetes mellitus.

OBJECTIVE: To compare the GI symptoms in diabetic patients with controls and its relationship with the complications, duration of diabetes and glycaemic control. METHODS: Consecutive patients were prospectively enrolled in to two groups. Group I (diabetic patients) and Group II (non-diabetic, Controls). Patient's characteristics, demographic profiles and GI symptoms were evaluated on a questionnaire. Groups were compared for differences in various GI symptoms. Group I was further analyzed for the relationship between GI symptoms with complications, duration of diabetes and glycaemic control. RESULTS: A total of 514 patients were enrolled 250 were diabetics (group I) and 264 were non-diabetics (group II). Mean age was 51.8 +/- 10.6 years and 50.2 +/- 9.2 years in groups i and ii respectively. All GI symptoms; heartburn, dyspepsia, bowel related abdominal pain, diarrhea, constipation, and faecal incontinence were significantly more in diabetics than controls (P < .5). The presence of diabetic neuropathy, retinopathy and HbAlc of > 7 were significantly (P < .5) related to GI symptoms. Duration of diabetes (>10 years) was not found significantly linked to GI symptoms. CONCLUSIONS: GI symptoms in diabetics were more frequent then control subjects and were significantly associated with poor glycaemic control, neuropathy and retinopathy but not with duration of diabetes. Number of GI symptoms increases with the severity of poor glycaemic control in diabetic patients

Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial.

OBJECTIVE: To study whether prophylactic theophylline can reduce the incidence and/or severity of renal failure in term infants with perinatal asphyxia. STUDY DESIGN: Term neonates with severe perinatal asphyxia were randomized to receive a single dose of either theophylline (study group, n = 40) or placebo (control group, n = 30) during the first hour of life. Daily weight, output/input ratio, 24-hour fluid intake, and urine volumes were recorded during the first 5 days of life. Those infants with asphyxial renal failure were followed up for 1 year. RESULTS: The incidence of severe renal dysfunction was increased in the control group. Creatinine clearance was higher and excretion of beta 2 microglobulin (beta2M) was lower in the theophylline group. Conversely, the glomerular filtration rate was lower in the control group. In infants with renal failure, serum creatinine and creatinine clearance returned to normal in the neonatal period, and the increased beta2M excretion normalized by age 6 weeks. CONCLUSIONS: A single dose of theophylline within the first hour of birth in term neonates with perinatal asphyxia results in a significant decrease in serum creatinine level and urinary excretion of beta2M, along with an increase in creatinine clearance.

Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga maritima.

DHFR (dihydrofolate reductase) catalyses the metabolically important reduction of 7,8-dihydrofolate by NADPH. DHFR from the hyperthermophilic bacterium Thermotoga maritima (TmDHFR), which shares similarity with DHFR from Escherichia coli, has previously been characterized structurally. Its tertiary structure is similar to that of DHFR from E. coli but it is the only DHFR characterized so far that relies on dimerization for stability. The midpoint of the thermal unfolding of TmDHFR was at approx. 83 degrees C, which was 30 degrees C higher than the melting temperature of DHFR from E. coli. The turnover and the hydride-transfer rates in the kinetic scheme of TmDHFR were derived from measurements of the steady-state and pre-steady-state kinetics using absorbance and stopped-flow fluorescence spectroscopy. The rate constant for hydride transfer was found to depend strongly on the temperature and the pH of the solution. Hydride transfer was slow (0.14 s(-1) at 25 degrees C) and at least partially rate limiting at low temperatures but increased dramatically with temperature. At 80 degrees C the hydride-transfer rate of TmDHFR was 20 times lower than that observed for the E. coli enzyme at its physiological temperature. Hydride transfer depended on ionization of a single group in the active site with a p K(a) of 6.0. While at 30 degrees C, turnover of substrate by TmDHFR was almost two orders of magnitude slower than by DHFR from E. coli; the steady-state rates of the two enzymes differed only 8-fold at their respective working temperatures.

Effect of amino acids on inhibition of lactate dehydrogenase-X by gossypol

Gossypol acetic acid (GAA) has been shown to have male antifertility effects, but there are pronounced differences among animal species. In the search of endogenous effector molecules, which interfere with the functions of GAA, we have studied the in vitro effect of various amino acids on the inhibition of the purified LDH-X by GAA. Histidine, cysteine and glycine were shown to block the effect of GAA. The effects of these amino acids were concentration dependent. Histidine and glycine protection was found to be complex type in which both the Km and Vmax were decreased compared to control. Arginine, glutamic acid, phenylalanine and valine were found to be ineffective against the inhibitory action of GAA.

Purification and characterization of lactate dehydrogenase from Varanus liver

Lactate dehydrogenase was purified 21-fold from liver of Varanus bengalensis using colchicine-sepharose column chromatography. The crude enzyme showed two isoenzymes (LDH-5 and LDH-4) by agarose gel electrophoresis (AGE). The purified enzyme showed a single band after SDS-PAGE corresponding to molecular mass of 35 kDa. The molecular mass of native enzyme was about 140 kDa. The optimum pH for the forward reaction was 7.5 while that for the reverse reaction was pH 9.5. The K-m values for pyruvate, NADH, lactate and NAD(+) were 0.17 +/- 0.037, 0.02 +/- 0.004, 12.4 +/- 3.05 and 0.38 +/- 0.032 mM, respectively. Pre-heating of enzyme showed that its t(50) was 40-50 degrees C. Oxalate and n-hexanediol were inhibitors for both forward and reverse reactions. Among divalent ions, Cu++ was shown to be more effective inhibitor for the forward reaction.

Serum lipid profile in Kashmiri children.

314 normal children in the age group of 5-14 years including 169 boys and 145 girls, were studied for their blood lipids and lipoprotein levels. Mean total cholesterol (Tch) of 172.8 mg/dl, triglycerides (TG) of 66.4 mg/dl, high density lipoprotein (HDLc) of 71.2 mg/dl, low density lipoprotein (LDLc) of 88.9 mg/dl and very low density lipoprotein (VLDLc) of 13.3 mg/dl was obtained. Lipid profile did not show any significant correlation with age and sex. Serum Tch and LDLc were higher in upper socio-economic group (P < 0.01). Tch and LDLc were higher in children taking high percentage of calories from fat and consuming more animal fats (P < .01) while HDLc value had an inverse relationship to these dietic rations.

Relationship between protein adsorptive capacity and the X-ray diffraction pattern of aluminium hydroxide adjuvants.

Thermal treatment during the preparation of aluminium hydroxide adjuvants affects the primary crystallite size of the adjuvant. The primary crystallite size can be characterized by the line broadening of the (020) reflection of the X-ray diffraction pattern. Studies of protein adsorption using bovine serum albumin as a model protein revealed a direct relationship between the albumin adsorptive capacity and the width at half height (WHH) of the (020) reflection in the X-ray diffraction pattern.

Characterization of antacid compounds containing both aluminum and magnesium. II. Codried powders.

The composition and antacid properties of six samples of codried antacids containing both aluminum and magnesium were determined. Aluminum hydroxide-magnesium carbonate codried gel and aluminum hydroxide-magnesium hydroxide codried gel were non-homogeneous, as the samples contained combinations of hydrotalcite, amorphous aluminum hydroxide, magnesium hydroxide, magnesium hydroxycarbonate, and magnesium carbonate. All samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett-Rice test.

Characterization of antacid compounds containing both aluminum and magnesium. I. Crystalline powders.

The composition and antacid properties of 10 samples of crystalline antacids containing both aluminum and magnesium were determined. The composition was found to vary significantly, even within the same type of antacid. For example, three of four hydrotalcite samples exhibit evidence of the presence of a minor phase of amorphous aluminum hydroxide. Almagate and almagcit, which are claimed to be unique compounds, were found to be composed of hydrotalcite, magnesium hydroxycarbonate, and/or magnesium carbonate and amorphous aluminum hydroxide. All three magaldrate samples examined contained a minor phase of amorphous aluminum hydroxide. All 10 samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett-Rice test.

Persistent limb pain and raised serum alkaline phosphatase the earliest markers of subclinical hypovitaminosis D in Kashmir.

The present study was an attempt to assess the cause of persistent pain in lower limbs among children from Kashmir. The study was conducted on one hundred children attending Paediatric out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar. All the children were in the age group of 5 to 14 years. They showed markedly raised levels of serum alkaline phosphatase, whereas serum phosphorus, serum calcium levels and antistreptolycin O-titres were normal in 93% cases. None of them had any rheumatic or rheumatoid pathology. Among 15 suspected clinical rickets only three were established radiologically. Dietary and socio-economic history revealed deficient vitamin D intake and less exposure to sun. It was hypothesized that sub-clinical vitamin D deficiency could be a major cause of persistent pain in lower limbs and raised serum alkaline phosphatase could be the earliest marker of vitamin D deficiency. It was confirmed by injecting single dose of vitamin D (3 lac I. U.) which relieved bone pain and lowered the levels of serum alkaline phosphatase to normal within 14 weeks of initiation of therapy.