Differences in glycinergic mIPSCs in the auditory brain stem of normal and congenitally deaf neonatal mice

We have investigated the fundamental properties of central auditory glycinergic synapses in early postnatal development in normal and congenitally deaf (dn/dn) mice. Glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded using patch-clamp methods in neurons from a brain slice preparation of the medial nucleus of the trapezoid body (MNTB), at 12-14 days postnatal age. Our results show a number of significant differences between normal and deaf mice. The frequency of mIPSCs is greater (50%) in deaf versus normal mice. Mean mIPSC amplitude is smaller in deaf mice than in normal mice (mean mIPSC amplitude: deaf, 64 pA; normal, 106 pA). Peak-scaled fluctuation analysis of mIPSCs showed that mean single channel conductance is greater in the deaf mice (deaf, 64 pS; normal, 45 pS). The mean decay time course of mIPSCs is slower in MNTB neurons from deaf mice (mean half-width: deaf, 2.9 ms; normal, 2.3 ms). Light- and electron-microscopic immunolabeling results showed that MNTB neurons from deaf mice have more (30%) inhibitory synaptic sites (postsynaptic gephyrin clusters) than MNTB neurons in normal mice. Our results demonstrate substantial differences in glycinergic transmission in normal and congenitally deaf mice, supporting a role for activity during development in regulating both synaptic structure (connectivity) and the fundamental (quantal) properties of mIPSCs at central glycinergic synapses.     

The calcium ion dependence of scallop myosin ATPase activity

Summary The ATPase activity of scallop (Pecten maximus) striated adductor myosin and heavy meromyosin (HMM) have been investigated as a function of [Ca²⁺] using formycin triphosphate (FTP) as a fluorescent ATP analogue. The FTPase activity of the regulated fraction of these preparations was activated steeply over the range of 0.1 to 1M [Ca²⁺ ], implying the existence of a form of cooperativity that is intrinsic to the myosin heads. In addition to the previously characterised heterogeneity with respect to an unregulated fraction, the regulated fraction of HMM was resolved into two populations whose activities showed a slightly different dependency on [Ca²⁺ ]. This was revealed unambiguously at intermediate levels of activation where, in some experiments, the product release rate constants differed for the two populations by more than fivefold. At maximum relaxation or maximum activation, these rate constants differed by two-to three-fold and were not clearly resolved by the multiexponential fitting procedure. The populations might arise as a consequence of isoenzymes, modification during preparation or slowly interconverting conformers; Ca²⁺ binding itself being a rapid equilibrium process in both populations. FTP turnover by myosin could not be analysed in such detail because of the technical problems of measuring the fluorescence of a suspension of filaments, but the rates of the elementary steps appeared similar to those of HMM. The fraction of unregulated molecules in myosin preparations was comparable to that of HMM indicating that if it is a consequence of preparative damage, the modification must occur prior to tryptic digestion.     

Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. Panretin Gel North American Study Group

BACKGROUND: Kaposi's sarcoma (KS) is the most frequent malignancy in patients with HIV. Given the promise that retinoids show in the treatment of various hyperproliferative skin disorders and in vitro evidence of inhibition of proliferation of KS cells, a randomized, controlled clinical trial was conducted. METHODS AND RESULTS: A 12-week, multicenter, randomized, double-blind, vehicle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determined by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Of 268 patients entered in the blinded treatment phase of the study (alitretinoin group, n = 134; vehicle group, n = 134), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive response, compared with 24 patients (18%) treated with vehicle gel. Of 184 patients receiving open-label alitretinoin treatment following the blinded phase of the trial, 90 patients (49%) met criteria for a positive response. This superior efficacy of alitretinoin gel over vehicle gel was maintained when the data were adjusted or analyzed for age, race, Kamofsky scores, baseline CD4+ lymphocyte counts, number of raised lesions at baseline, and aggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies. Most adverse events were mild to moderate in severity, limited to the application site, and reversible on reduction in frequency or suspension of application. Relatively few patients (7%) discontinued alitretinoin therapy because of to related adverse events. CONCLUSIONS: The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoin 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS lesions.     

Ameliorating effect of microdoses of a potentized homeopathic drug,Arsenicum Album,on arsenic-induced toxicity in mice

Background  

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.     

A mathematical model of optimized radioiodine-131 therapy of Graves' hyperthyroidism

Background

The current status of radioiodine-131 (RaI) dosimetry for Graves' hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic hypothyroidism are two problems which interact such that trying to solve one leads to exacerbation of the other. Optimized RaI therapy has therefore begun to be defined just in terms of early hypothyroidism (ablative therapy) as physicians have given up on reducing hypothyroidism.

Methods

Optimized therapy is evaluated both in terms of the greatest separation of cure rate from hypothyroidism rate (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by mathematical modeling of outcome after radioiodine and critically discussing the three common methods of RaI dosing for Graves' disease.

Results

Cure follows a logarithmic relationship to activity administered or absorbed dose, while hypothyroidism follows a linear relationship. The effect of including or omitting factors in the calculation of the administered I–131 activity such as the measured thyroid uptake and effective half-life of RaI or giving extra compensation for gland size is discussed.

Conclusions

Very little benefit can be gained by employing complicated methods of RaI dose selection for non-ablative therapy since the standard activity model shows the best potential for cure and prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides the best outcome in terms of cure and early hypothyroidism.     

Quantitative method for determining serum alkaline phosphatase isoenzyme activity II. Development and clinical application of method for measuring four serum alkaline phosphatase isoenzymes.

A method for quantitating the liver, bone, intestinal and placental alkaline phosphatase activity of serum, using an algorithm for converting selective inactivation by guanidine hydrochloride, L-phenylalanine, and heat into equivalent isoenzyme activity is described. The method can individually quantify mixtures of isoenzymes to within a margin of 3%; it has acceptable reproducibility and has been used to develop both age and sex related reference ranges. Analysis time is about 30 minutes. The clinical reliability of this method has been shown in a study of 101 patients, in 79% of whom isoenzyme results were compatible with the final clinical diagnosis; in 10% a clinical diagnosis resulted from isoenzyme analysis, and in a further 11% the source of the increased alkaline phosphatase activity was identified and supported by electrophoresis, with a definite clinical diagnosis yet to be made.     

A comparative study of the torque generated by the shoulder internal and external rotator muscles in different positions and at varying speeds

The torque generated by the shoulder internal and external rotator muscles duringconcentric isokinetic contractions has been investigated. Recordings were made in three positions: neutral, 90 degrees of flexion, and 90 degrees of abduction; and at three speeds of contraction (60, 120, and 180 /sec) in each of these positions. Twelve healthy female university students were randomly selected from a 100 female volunteer population. Testing was accomplished using an isokinetic dynamometer. A two-way analysis of variance for position and speed was conducted. The greatest torque values for the internal rotator muscles were achieved in the neutral position, while maximum values for the external rotators were developed in 90 of shoulder flexion. The test speed of 60 degrees /sec was shown to produce the highest torque values for the external rotator muscles. However, no difference in test speeds of contraction was found when analyzing the torque values generated by the internal rotator muscles. Implications for strength training are discussed.J Orthop Sports Phys Ther 1987;9(6):217-222.     

改良尿道拖入术治疗外伤性后尿道狭窄

自1994年以来,我院采用改良的尿道拖人术治疗外伤性后尿道狭窄22例,取得满意疗效,现报道如下。l临床资料本组病例均为男性,为严重车祸伤或高处跌伤致骨盆骨折所致,年龄则一46岁,平均35岁。临床症状有尿道四溢血、尿摊留、腹胀、肛周青紫肿胀,有休克者2例,合并直肠损伤2例,磅眈破裂6例。术中发现前列腺尖游离者4例。所有病例不能将导尿管插入膀跳,而均行单纯“耻骨上膀胜造疾术”,有膀脱破裂者行“膀脱破裂修补术”,有直肠损伤者,行“乙状结肠造疫术”。患者于术后3－6个月来院行尿道重建术。术前常规尿道造影,显示膜部尿道狭…     

Which Parameters Affect Biofilm Removal with Acoustic Cavitation? A Review

Bacterial biofilms are a cause of contamination in a wide range of medical and biological areas. Ultrasound is a mechanical energy that can remove these biofilms using cavitation and acoustic streaming, which generate shear forces to disrupt biofilm from a surface. The aim of this narrative review is to investigate the literature on the mechanical removal of biofilm using acoustic cavitation to identify the different operating parameters affecting its removal using this method. The properties of the liquid and the properties of the ultrasound have a large impact on the type of cavitation generated. These include gas content, temperature, surface tension, frequency of ultrasound and acoustic pressure. For many of these parameters, more research is required to understand their mechanisms in the area of ultrasonic biofilm removal, and further research will help to optimise this method for effective removal of biofilms from different surfaces.