Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects

Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p?=?0.005) as well as after water (1 [0-14], p?=?0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p?=?0.0001) and after water (34 [15-67] mmHg, p?=?0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects.     

CdTe QD-based inhibition and reactivation assay of acetylcholinesterase for the detection of organophosphorus pesticides

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides. In principle, GSH-capped CdTe QDs exhibit higher sensitivity towards H₂O₂ produced from the active enzymatic reaction of acetylcholinesterase (AChE) and choline oxidase (CHOx), which results in the fluorescence (FL) “turn-off” of the GSH-capped CdTe QDs. A “turn-on” FL of the CdTe QDs at 520 nm was recovered in the presence of organophosphate (OP). The FL changes of the GSH-capped CdTe QD/AChE/CHOx biosensor reasonably correspond to the amount of OP pesticides. The detection limit of the CdTe/AChE/CHOx biosensor towards paraoxon, dichlorvos, malathion and triazophos was 1.62 × 10⁻¹⁵ M, 75.3 × 10⁻¹⁵ M, 0.23 × 10⁻⁹ M and 10.6 × 10⁻¹² M, respectively. The GSH-capped CdTe QDs/AChE/CHOx biosensor was applied as a FL nanoprobe for assaying the enzymatic activity of AChE. The inhibited AChE was reactivated up to 94% using pyridine oximate (2-PyOx⁻), and functionalized pyridinium oximates (4-C₁₂PyOx⁻ and 4-C₁₈PyOx⁻) of varying chain lengths. It was found that the reactivation potency of the tested oximes varied with the chain length of the oximes. This biosensing system offers the promising benefit for the determination of the OP pesticides in food, water and environmental samples.

An enzyme immobilized glutathione (GSH)-capped CdTe quantum dot (QD)-based fluorescence assay has been developed for monitoring organophosphate pesticides.     

Design, synthesis, and evaluation of isoniazid derivatives acting as potent anti-inflammatory and anthelmintic agents via Betti reaction

A novel synthesis of isoniazid derivatives achieved by the condensation of aldehydes, isoniazid, and phenols via Betti reaction has been described. The reactions were carried out at room temperature using fluorite as catalyst. The catalyst is efficient, benign, reusable, cost-effective, and ecofriendly. The novel synthesized moieties were characterized on the basis of ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. All the synthesized agents 4(a–j) were examined for their potential in vivo anti-inflammatory activity on Wistar albino rats using a standard reference drug, diclofenac. These synthesized derivatives were further screened for their potent in vitro anthelmintic activity using a standard reference drug, albendazole on Indian earthworms, Pheretima posthuma. A correlation of structure and activity relationship of these compounds with respect to Lipinski’s rule of five, drug likeness, toxicity profiles, and other physico-chemical properties of drugs is described.     

Effect of acute and long-term oral tobacco use on oesophageal motility

BACKGROUND AND AIMS: Nicotine administration is known to decrease lower oesophageal sphincter (LOS) pressure. Although a few studies have assessed the effect of tobacco on the LOS, the effect of acute and long-term oral tobacco use on oesophageal motility is not known. The study was designed to investigate the effect of acute and long-term oral tobacco use on LOS and distal oesophageal motility. METHODS: Thirty-six healthy men (aged 18-65 years, median 34 years; 18 oral tobacco users, 18 non-tobacco users) underwent oesophageal manometry using a water-perfusion system. After baseline manometry, tobacco users were asked to keep 0.5 g tobacco in their mouth for 10 min; non-users of tobacco were kept in quiet surroundings for a similar period. Manometry was then repeated. RESULTS: The LOS basal pressures were similar in tobacco users and non-tobacco users (mean +/- SD 15.4 +/- 6.3 vs 13.4 +/- 5.3 mmHg). In the distal oesophageal body, the velocity (4.4 +/- 3.1 vs 4.9 +/- 2.6 cm/s), amplitude (92.7 +/- 38.3 vs 84.8 +/- 33.2 mmHg) and duration of contraction (2.1 +/- 0.7 vs 1.7 +/- 0.9 s) were similar in tobacco users and non-users. Acute tobacco use did not affect these parameters. The numbers of abnormal waves (triple peaks and non-transmitted contractions) were also similar in the two groups. CONCLUSION: Oral tobacco use does not appear to affect LOS pressures and distal oesophageal motility acutely or in the long term.     

Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in anti-inflammatory activity and reduction in ulcerogenicity in rats

Ketorolac, is a non-steroidal anti-inflammatory drug, with strong analgesic activity. It is practically insoluble in water and has been implicated in causing gastrointestinal ulceration. This study describes the formulation of solid dispersions of ketorolac using hydroxypropyl beta-cyclodextrin (HPbeta-CyD) and beta-cyclodextin (beta-CyD) as carriers, to improve the aqueous solubility of the drug, thus enhancing its bioavailability. Also, reduction in ulcerogenicity was anticipated. Differential scanning calorimetry and X-ray diffraction studies indicated loss of crystalline nature of the drug, in the dispersions prepared with HPbeta-CyD. NMR studies revealed a strong interaction between drug and HPbeta-CyD. Solid dispersions of drug with beta-CyD retained the crystalline nature of the drug. All the solid dispersions showed a remarkable improvement in the rate and extent of dissolution of ketorolac. The kneaded dispersion with HPbeta-CyD prepared using a 1:1 alcohol-water mixture showed promise in reducing the ulcer-inducing effect of ketorolac in rats. Oral administration of this dispersion was found to inhibit carrageenan-induced paw oedema in rats to a significantly greater extent compared with ketorolac or its trometamol salt. Though beta-CyD as a carrier for ketorolac gave faster release of the poorly soluble drug, HPbeta-CyD proved to be superior to beta-CyD, as a carrier in the kneaded dispersion prepared using 1:1 alcohol-water mixture. These results suggest that solid dispersions of ketorolac with HPbeta-CyD aid in faster dissolution and better bioavailability of the drug. The higher solubility of the drug in the presence of HPbeta-CyD also reduces local gastrointestinal side-effects of the drug.     

Homicide by direct snake bite: a case of contract killing

It has been estimated that five million snake bite cases occur worldwide every year, causing about 100,000 deaths. Snake bite is exclusively accidental in nature. Suicide by snake bite is very rare and homicidal snake bite is not reported. In the present case, a contract killer was hired, who used a poisonous snake to kill an elderly couple by way of direct snake bite. We believe this to be the first case reported where a snake was directly used for the murder of two victims through a contract killer.     

Efficacy of nasolabial flap in reconstruction of fibrotomy defect in surgical management of oral submucous fibrosis: a prospective study

Purpose

Various surgical modalities have been used in the surgical management of oral submucous fibrosis with variable results. This prospective study evaluates the efficacy of nasolabial flap in the reconstruction of fibrotomy defect in surgical treatment of oral submucous fibrosis in terms of functional and esthetic outcomes.

Material and method

In this prospective study, we treated 20 patients of oral submucous fibrosis surgically. The surgical protocol was consisting of bilateral fibrotomy, temporal myotomy, and coronoidotomy or coronoidectomy followed by reconstruction of fibrotomy defect with bilateral extended nasolabial flaps. All patients were prescribed with nutritional supplements and antioxidants. Vigorous mouth opening exercise was made compulsory for every patient. Preoperative and postoperative evaluation was done for interincisal mouth opening, function of mastication, and cosmetic results. Patient’s regular follow-up was done for 2 years.

Results

Postoperatively, we noted excellent increase in the interincisal mouth opening relieving trismus. Patient’s ability to chew solid food was increased significantly. Extraoral scar was minimal and well accepted by all the patients. There was no morbidity of the donor site. There was no injury to the facial nerve in all cases. The only drawback was intraoral hair growth which went on reducing with mucosalization of the graft tissue.

Conclusion

Random pattern nasolabial flap is a very good option for intraoral reconstruction of fibrotomy defect in surgical treatment of oral submucous fibrosis with excellent functional and cosmetic results with minimal complications.

     

Pharmacokinetic/pharmacodynamic profiling of imipenem in patients admitted to an intensive care unit in India: A nonrandomized,cross-sectional,analytical, open-labeled study

Results:The difference in the plasma imipenem concentration between the gastrointestinal and the nongastrointestinal groups was significant at 2 h (P = 0.015) following drug dosing; while the difference was significant between the skin/cellulitis and nonskin/cellulitus groups at 2 h (P = 0.008), after drug dosing. The imipenem levels were above the MIC and 5 times the MIC for the isolated organism in 96.67% and 50% of the patients, respectively.Conclusions:The pharmacokinetic profile of imipenem does not vary according to the locus of an infection in critically ill patients. Imipenem, 3 g/day intermittent dosing, maintains a plasma concentration which is adequate to treat most infections encountered in patients admitted to an ICU. However, a change in the dosing regimen is suggested for patients infected with organisms having MIC values above 4 mg/L.