Neuroprotection in glaucoma

Currently, glaucoma is recognised as an optic neuropathy. Selective death of retinal ganglion cells (RGC) is the hallmark of glaucoma, which is also associated with structural changes in the optic nerve head. The process of RGC death is thought to be biphasic: a primary injury responsible for initiation of damage that is followed by a slower secondary degeneration related to noxious environment surrounding the degenerating cells. For example, retinal ishaemia may establish a cascade of changes that ultimately result in cell death: hypoxia leads to excitotoxic levels of glutamate, which cause a rise in intra-cellular calcium, which in turn, leads to neuronal death due to apoptosis or necrosis. Neuroprotection is a process that attempts to preserve the cells that were spared during the initial insult, but are still vulnerable to damage. Although not yet available, a neuroprotective agent would be of great use in arresting the progression of glaucoma. There is evidence that neuroprotection can be achieved both pharmacologically and immunologically. Pharmacological intervention aims at neutralising some of the effects of the nerve-derived toxic factors, thereby increasing the ability of the spared neurons to cope with stressful conditions. On the other hand, immunological interventions boost the body's own repair mechanisms for counteracting the toxic effects of various chemicals generated during the cascade. This review, based on a literature search using MEDLINE, focuses on diverse cellular events associated with glaucomatous neurodegeneration, and discusses some pharmacological agents believed to have a neuroprotective role in glaucoma.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Iodine deficiency disorders in Bangladesh

An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations. the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. An erratum to this article is available at .     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

几种中西药抗人实验模拟运动病效果观察

目的 :选用中药“治晕灵”的主要成分生姜、明天麻等六味草药煎成汤剂、或半量汤剂配西药脑益嗪、山莨菪碱各1 4临床常用量配成复方中西药制剂 ,与目前常用抗晕药晕海宁等中、西药的药效进行比较 ,看中药制剂或中西药复方制剂是否具有较好的抗运动病效果。方法 :选 7名敏感被试者 (女性 ,19～ 2 1岁 ) ,用旋转刺激诱发运动病至出现恶心。按拉丁方设计 ,与安慰剂 (淀粉 10 0mg)及晕海宁 (5 0mg)进行对比 ,分别观察了生姜合剂 (30ml)、晕可平 (30ml)、山莨菪碱 (10mg)、脑益嗪 (2 5mg)及上述复方中西药制剂口服后的运动病耐力。结果 :与安慰剂比较 ,晕海宁、山莨菪碱、脑益嗪、晕可平、生姜合剂、复方中西药制剂分别使运动病耐力提高 5 .4%、7.5 %、5 .9%、7.4%、32 .3 %、2 0 .4% ;生姜合剂效果较优 ,除口服时有辛辣味外 ,无明显的副作用。复方中西药制剂各成分未显示协同作用 ,而只是简单的作用相加。结论 :生姜合剂具有较好的抗运动病作用     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.