Gabapentin Activates Spinal Noradrenergic Activity in Rats and Humans and Reduces Hypersensitivity after Surgery

Background: Gabapentin has been reported to inhibit various acute and chronic pain conditions in animals and humans. Although the efficacy of gabapentin depends on the [alpha]2[delta] subunit of voltage-gated calcium channels, its analgesic mechanisms in vivo are still unknown. Here, the authors tested the role of spinal noradrenergic inhibition in gabapentin's analgesia for postoperative pain.

Methods: Gabapentin was administered orally and intracerebroventricularly to rats on the day after paw incision, and withdrawal threshold to paw pressure was measured. The authors also measured cerebrospinal fluid concentration of norepinephrine and postoperative morphine use after surgery in patients who received oral placebo or gabapentin.

Results: Both oral and intracerebroventricular gabapentin attenuated postoperative hypersensitivity in rats in a dose-dependent manner. This effect of gabapentin was blocked by intrathecal administration of the [alpha]2-adrenergic receptor antagonist idazoxan and the G protein-coupled inwardly rectifying potassium channel antagonist tertiapin-Q, but not by atropine. In humans, preoperative gabapentin, 1,200 mg, significantly increased norepinephrine concentration in cerebrospinal fluid and decreased morphine requirements.     

Diagnosis goes digital.

Accurate images of the craniofacial region are critical for the development of an orthodontic diagnosis and treatment plan. The NewTom QR 9000 Volume Scanner (QR s.r.l., Verona, Italy) represents a significant advance in imaging capabilities for dentistry and orthodontics. This new-generation scanner uses computed tomography technology to provide a complete 3D view of the maxilla and mandible with relatively high resolution and low radiation exposure to patients. This article discusses some technical aspects of this new scanner and its possible orthodontic uses.     

Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue glycogen content and in vitro release of insulin in streptozotocin induced diabetic rats.

The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats and compared with a known drug, tolbutamide. The oral effective dose (ED) of the extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6% (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous extract of T.chebula (AETC) daily once for two months reduced the elevated blood glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in controlling the elevated blood lipids as well as decreased serum insulin levels in contrast to the untreated diabetic animals. Hepatic and skeletal muscle glycogen content decreased by 75% and 62.9% respectively in diabetic controls, these alterations were partly prevented (34.9% and 21.17%) in AETC treated group when compared to the healthy controls. The in vitro studies with pancreatic islets showed that the insulin release was nearly two times more than that in untreated diabetic animals. The treatment did not have any unfavorable effect on other blood parameters of liver and kidney function tests. LD 50 was found to be above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even at this dose indicating high margin of safety. These findings suggest further investigations for the possible use of the aqueous extract of fruits of T.chebula for the treatment of diabetes.     

Pulmonary arteriovenous fistula in a patient with renal cell carcinoma.

Arteriovenous (AV) fistulas are common in renal cell carcinoma. These are usually small and asymptomatic. Case reports have previously described symptomatic fistulas in primary renal cell tumour or, less commonly, bone metastases. The current study describes a patient with lung metastases from renal cell carcinoma who developed a symptomatic pulmonary AV fistula. The patient presented with debilitating progressive shortness of breath, which resolved after coiling of the pulmonary AV fistula. Supporting radiographs include a unique ventilation-perfusion finding of perfusion tracer in the kidney that is diagnostic of a pulmonary shunt. This is the first report of a pulmonary fistula from renal cell carcinoma. This rare complication of renal cell carcinoma reflects its diverse clinical presentations and unique tumour biology.     

Recombinant glycoprotein based vaccine for Chandipura virus infection

Chandipura virus (CHPV) has emerged as an important pediatric encephalitis-causing pathogen with very high mortality in India. No specific vaccine or treatment is available till date. We attempted to prepare a candidate vaccine employing recombinant CHPV Glycoprotein (rGp). The Glycoprotein gene (G-gene) of CHPV was expressed using Baculovirus expression system. The rGp was purified by HPLC and used for mice immunization, 3 doses, and 4 weeks apart. One microgram rGp was found to be optimum. Sero-conversion was observed as early as 2nd week by detecting anti-CHPV IgG antibodies. Antibody titres were immunogen-concentration dependent. Intracerebral challenge of the immunized mice with 100 LD₅₀ of the homologous strain demonstrated 90% protection. In in vitro neutralization, antibodies from the immunized mice were able to neutralize heterologous viruses. There was 60% T cell proliferation observed against rGp in immunized mice. The study shows that rGp induces both arms of immune response and represents an ideal vaccine candidate for further evaluations.     

Biphasic Dose Response in Low Level Light Therapy

The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.     

Impact de l’estimation de la population affiliée à l’assurance-maladie sur le calcul de la prévalence pharmacologique du diabète à l’échelle régionale et territoriale

BackgroundData derived from Health Insurance databases are very useful for health observation. These data are however still underused, particularly for small local areas. This may be partly explained by the lack of reliable data on the number of insured people. Recent simplification of the Répertoire national interrégimes de l’assurance-maladie (RNIAM) indicator (French register of health insurance) gives the opportunity to improve the usefulness of these databases. This indicator specifies the beneficiaries’ status towards the General Health Insurance Fund. This study aimed to select the population of beneficiaries, which could be most adequately used to calculate health indicators based on these data.MethodsData were collected from the outpatient database of the Southeastern France General Health Fund. We compared beneficiaries’ characteristics according to the RNIAM indicator, calculated the annual unadjusted and age-adjusted regional and local prevalence of diabetes mellitus in two different populations: the whole initial beneficiaries database, and the population of “effective” beneficiaries (persons whose reimbursements were effectively managed by the General Health Insurance).ResultsThe initial database included 4,817,871 beneficiaries. Almost 80% were in the “effective” population, 14% had left the General Health Insurance, or Southeastern France, and 4% were doubles. The annual unadjusted prevalence of diabetes mellitus was 3.31% in the initial database, and more than 20% higher when calculated among “effective” beneficiaries. Impact on aged-adjusted prevalence was less important (+9% at regional level), but the increase varied from 6 to 42% for the small local areas. Impact was much higher on age and gender specific rates.ConclusionWhen Health Insurance databases are used to calculate health indicators at various geographical levels, only “effective” beneficiaries should be selected. The methodology for determining health indicators might be improved by updating databases (e.g. the date of the RNIAM indicator last update should be added).