Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development.

The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed.

A Study on Pulmonary Complications of Systemic Sclerosis in Eastern India.

Aim. This study was undertaken to find out the characteristics of clinical, radiological and functional changes affecting the respiratory system in patients with systemic sclerosis (SSc) from eastern India, and the association of these characteristics with pulmonary hypertension. Methods. This was a cross-sectional, observational study involving 46 patients. Other than the routine tests, anti-nuclear antibody (ANA), spirometry, diffusing capacity of lung for carbon monoxide (DLCO) measurement, chest radiograph, highresolution computed tomography (HRCT) of thorax, 6-minute walk test and echocardiography were done. Results. Out of a total of 46 patients, 27 patients had diffuse cutaneous SSc (dcSSc) and 19 had limited cuteaneous SSc (lcSSc). Eleven patients had pulmonary hypertension. The HRCT revealed diffuse parenchymal lung disease (DPLD) in 32 (65%) cases. The ANA was positive in 83% cases. Anti-Scl70 was found in 41% of patients with dcSSc and anti-centromere antibody was found in 47% of patients with lcSSc. Spirometry revealed restrictive pattern in 30 patients; 9 had obstruction; and the rest were normal. The DLCO was abnormal in 38 patients. A strong correlation was found between reduction in DLCO and pulmonary artery systolic pressure (PASP). Also, a strong association was observed between a drop of >4% in oxygen saturation on 6-minute walk test and presence of pulmonary arterial hypertension (PAH). Conclusions. Majority of the patients with SSc had restrictive lung disease with abnormal DLCO and features resembling non-specific interstitial pneumonia. Nucleolar ANA was predominantly found in patients having PAH. Presence of DPLD had a negative association with presence of anti-centromere antibody. Reduction in DLCO and a fall of >4% in oxygen saturation on 6-minute walk test may be used as predictors of PAH in asymptomatic individuals.

Ectopic thyroid tissue- A case series

@#<p><strong>OBJECTIVE:</strong> To describe the clinical presentation and course of seven ectopic thyroid patients. <br /><br /><strong>METHODS:<br />Design:</strong> Retrospective Chart Review<br /><strong>Setting:</strong> Tertiary Government Teaching Hospital<br /><strong>Patient:</strong> Seven patients<br /><br /><strong>RESULTS:</strong> Five patients were female and two were male (ratio of 5:2). Three belonged to the 20 to 30 year-old age group, whereas two were below 10 years of age. All seven were biochemically hypothyroid and ectopic thyroid was found to be the only functioning thyroid tissue. Three patients were managed medically with levothyroxine, while ectopic thyroid was excised in four. Ectopic thyroid tissue was autotransplanted in two cases following excision.<br /><br /><strong>CONCLUSION:</strong> The ages of presentation in the present series correspond with the increased physiological demand of thyroid hormone. Thyroid substitution therapy is a must in the presence of clinical and/or biochemical hypothyroidism. Surgical excision should be avoided as far as possible especially if the ectopic tissue is the only functioning thyroid in the body. Surgery is required in selected cases presenting with obstructive symptoms or hemorrhage which are unresponsive to substitution therapy. Auto transplantation of the ectopic thyroid may not provide significant benefit to the patient and more research is warranted in this aspect.</p>

T11 target structure exerts effector function by activating immune cells in CNS against glioma where cytokine modulation provide favorable microenvironment.

Glycoprotein T 11 target structure (T11TS), derived from sheep erythrocyte membrane, directly interacts with T cells to activate them to enter in the brain. When untreated, glioma exerts an immune-suppressive environment in its vicinity by secreting prostaglandin E2 (PGE2), IL-10, tumor growth factor , gangliosides etc. to dampen the immune attack. But exogenous administration of T11TS reverses the situation to pro-inflammatory immune active state by expressing enhanced IL-12 and tumor necrosis factor (TNF-) production and suppression of IL-4 and IL-10 levels. The T11TS activated lymphocytic accumulation along the capillary endothelium in brain and their penetration in the matrix was evident from histological sections. IL-6 with TNF- facilitates leukocyte migration to glioma site to exert cytotoxic effector function. Brain infiltrated lymphocytes offer cytotoxic proximity to neoplastic glial cells, which lead them to apoptosis. In the Th1 dominated microenvironment microglial cells was found with enhanced phagocytic functions. Initially infiltrated lymphocytes with microglia showed increased production of TNF-, interferon (IFN-) to facilitate their effector actions. Repeated dosing of T11TS shows glioma abrogation in rat model, but also a resurgence of anti-inflammatory cytokine environment found with increased IL-4, IL-10 and decreased IL-12, IL-6, TNF-. This is a unique homeostatic regulation of total immune system after T11TS mediated carnage of glioma. The resultant balance of cytokines between interacting glioma cells, T cells and microglia in T11TS induced condition determines the success of its immunotherapeutic effect in glioma.

Orbital and para-orbital tumours--a 10 years retrospective study.

A total number of 631 cases of orbital and para-orbital tumours causing proptosis was analysed in a retrospective way in relation to age, anatomic location, histological and clinical profile. CT-scan was considered as the primary modality of investigation as it correctly delineates the extent of the tumour, integrity of bony structures and intracranial spread. Different modalities of surgery like lateral orbitotomy, medial orbitotomy, lateral rhinotomy and endoscopic excision, etc, had been performed depending upon the anatomical locations. Surgical approaches, histological types of various tumours are analysed in detail.

Sheep erythrocyte demonstrated better effect than IL-2 and IFN-gamma as biological response modifier against glioma in experimental model.

The significant insights into the immunobiology of central nervous system (CNS) and brain tumor have opened up the feasibility of applying 'Immunotherapy' as an alternative to the poor prognosis of malignant brain tumor with conventional therapeutic approaches. Though cytokines like IL-2 and IFN-gamma used against glioma showed some favorable results by eliciting Th1 type immune response, a proper immunotherapeutic agent is still to be searched for. Sheep erythrocyte (SRBC), a corpuscular antigen showed a better therapeutic efficacy in terms of enhanced survival and augmentation of cell mediated immunity (CMI) in a glioma model developed by chemical carcinogen ethyl nitrosourea. Histological findings revealed most efficient glioma rejection in SRBC and combination biological response modifier (BRM) treated groups. Simultaneously E-rosetting, cytotoxicity of lymphocytes, phagocytosis and antigen presenting capacity of myeloid cells established the better therapeutic efficacy of SRBC alone than other BRMs viz. IL-2 and IFN-gamma. Even the effect of combination therapy of different BRMs showed marginal differences in facilitating glioma reduction than the single use of SRBC. These findings emphasized the application of SRBC as an exogenous BRM having the potential as a rational therapeutic adjunct against glioma.

The first cross sectional survey on intracranial malignancy in Kolkata, India: reflection of the state of the art in southern West Bengal.

Recent increase in the occurrence of intracranial malignancies and poor performance of therapeutic measures have established the disease as an important concern of medical sciences. The lack of information about the disease pattern throughout India creates problems for maintaining community health for prevention. The present study on the hospital population of Kolkata was conducted to determine the incidence pattern of the disease in the population of southern West Bengal, focusing on distribution with age, sex, occupation and religion in different districts of the region, and characterizing diagnostic and therapeutic measures. Among a total of 39,509 cancer patients from 21 health centers of Kolkata, 2.4% had brain cancers and among these more than 60% are gliomas. A cross-sectional study for a period of 3 years reported the occurrence of 15 types of intracranial malignancy, which demonstrated astrocytomas (36.8%), glioblastoma multiforme (GBM) (7.9%) and meningiomas (11.6%) to be predominant. Brain tumors occur more frequently in males with few exceptions and the incidence was found to be highest among the 40-49 year old group (20.2%). No specific trend for religion and occupation was apparent. However, the district wise distribution showed maximum incidences among industrial areas, namely, Kolkata (33.1%), North 24-Parganas (18.2%), Howrah (9.3%) and Hoogly (7.6%). Diagnosis of the disease was by CT scan, MRI and histological identification (pre and post operative). Therapeutic procedures rely mainly on surgery and radiotherapy, whereas chemotherapy was used as an adjuvant for about 10% of the cases. Evaluation of the scenario regarding intracranial malignancy in this region was a long awaited requirement which should ultimately serve an important function in pointing to risk zones within the population and allow better control measures to be introduced for the disease.

New drugs in India over the past 15 years: analysis of trends.

BACKGROUND: New drugs are appearing in the Indian pharmaceutical market every day. To study the trends we analysed the pattern of new drug approvals and introductions in India over the past 15 years (1988-2002). METHODS: Lists of new drugs approved by the Drugs Controller General of India, released half-yearly, were obtained and entered into a computer database. Additional information, such as anatomical therapeutic chemical coding, availability status till 31 December 2002 and source were added to this database before analysing overall time trends and the situation in individual therapeutic categories. RESULTS: Excluding unrecognized and compound formulations and 28 veterinary products, 396 drugs were approved for clinical use during this period. Of these, 315 have also been launched in the market and 5 were subsequently withdrawn. Nervous system-related drugs accounted for the largest number of approvals (82), followed by antimicrobials (73) and cardiovascular drugs (57). Five new antimalarials have emerged but other tropical diseases have been mostly ignored. Eleven vaccines have been added. CONCLUSION: There has been a sharp spurt in the annual number of approvals and introductions. The proliferation of brands and fixed-dose combinations has kept pace with the introduction of new molecules. Unfortunately, most new drugs are not major therapeutic advances. In the context of this rapid proliferation, meeting the information needs of prescribers, establishing an effective nationwide pharmacovigilance system and reorienting the focus of pharmacology education--from information provision to development of self-learning and critical judgement skills-are some issues for concern.