Studies on the interactions of copper and cannabis

The action of copper (CuSO₄, 5mg/kg, oral) on selected neuropharmacological actions of cannabis resin (CI, oral) was studied on albino rats and mice. Copper potentiated the barbiturate hypnosispotentiating activity of CI in albino rats and mice and had no effect on hypothermic activity in albino rats.Single doses of copper partially inhibited tolerance to barbiturate hypnosis-potentiation activity and markedly delayed the development of tolerance to hypothermic activity of CI. Oral as well as i.c.v. copper (CuSO₄, 0.1 g) in single dose antagonised the tolerance to hypothermic activity of cannabis or THC for to two weeks. Copper-CI interaction could be antagonised by penicillamine. Zinc (ZnSO₄, 5 mg/kg, oral) had an action similar to that of copper in antagonising the development of tolerance to the hypothermic activity of CI, but magnesium (MgSO₄, 5 mg/kg, i.p.) was devoid of any such action.Studies indicate that, although copper has no significant neuropharmacological action, it interacts with CI activity, especially in tolerant rats, in effects on hypothermia. The site of action of copper is possibly the hypothalamus, where it inhibits the processes of tolerance development to CI on the noradrenergic neurone.     

Pacemaker failure resulting from radiation damage

The authors present a case of radiation-induced pacemaker failure. After 2,000 rad (20 Gy) of photon irradiation for metastatic bronchogenic carcinoma, the pulse generator circuitry failed, producing a "runaway" rhythm. This suggests that present pacemaker circuitry may be more susceptible to irradiation than previously believed, and that even modest radiation doses can induce life-threatening arrhythmias.     

Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells

The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in anin vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabaln were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-@#@ 7.4 at 37°C and is not inhibited by the ATPase inhibitor ouabaln. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation fallure seen in this disease.     

Primary angiitis of CNS : neuropathological study of three autopsied cases with brief review of literature

Primary angiitis of CNS(PACNS) or granulomatous angiitis of CNS is a rare inflammatory disease of small blood vessels mostly confined to the CNS. The clinical and pathological features of 3 autopsied cases are described. Clinically all the three PACNS patients were young males, age ranging from 19 to 31 years. All presented with varied neurological manifestations. There was no evidence of systemic disease in any of the cases. The ESR was normal and CSF analysis showed chronic meningitic pattern. The cerebral angiogram in one case was normal and the CT scan done in another case showed multiple intracerebral haematoma due to vasculitis. Brain biopsy was not done. Diagnosis was made at post-mortem examination. Histology showed characteristic but variable degree of granulomatous and non-granulomatous angiitis of small vessels. Venulitis with parenchymal haemorrhages was the predominant feature and in one case phlebitis with thrombosis was noted. Since the disease responds to steroids and immunosuppressive therapy, establishing antemortem diagnosis is important. In view of the association of angiitis of CNS with bacteria and viral infections, their role in the evolution of the disease needs to be investigated.     

Endocrine effects of dehydroepiandrosterone and its fluorinated analog,fluasterone, in rats

Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fl‐DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fl‐DHEA has hormonal actions. The endocrinologic effects of DHEA and fl‐DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300 mg/kg/day for each drug (n=12/sex/group), which are equivalent to 104 and 1,042 µmoles/kg/day DHEA, and 103 and 1,034 µmoles/kg/day fl‐DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 µmoles/kg/day DHEA and fl‐DHEA, respectively). Administration of DHEA resulted in dose‐dependent increases in plasma DHEA and DHEA‐S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl‐DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl‐DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl‐DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. Drug Dev. Res. 58:169–178, 2003. © 2003 Wiley‐Liss, Inc.     

Balanitis xerotica obliterans – a review

Balanitis xerotica obliterans (BXO) is a scarcely known disease, wrongly considered rare. With a high degree of suspicion and histologic examination, the condition will prove to be much more frequent than one generally believes. The etiology of the condition is unknown at present. Many cases of BXO occurring after circumcision may be cases of secondary phimosis due to BXO not being recognized at the time of surgery. Most of the cases of BXO are seen in the third to fifth decades of life, even though they may occur at the extremes of age. Biopsy of the lesions is not essential in all cases and is indicated to differentiate from penile cancer and in atypical cases. Early diagnosis and treatment of BXO are very important in preventing the urological complications of the diseases such as urethral stricture. Treatment of BXO depends on the anatomic location of the lesions and their extent and severity, together with the rapidity of progression of the disease process. The treatment may vary from topical corticosteroids, laser vaporization in early cases to meatoplasty and urethroplasty in extensive cases. Topical pharmacotherapy is useful in the early stages to reduce the initial symptoms and slow down the progression, but is not effective in all cases and is not the curative treatment of disease. Meatal stenosis, phimosis, scar adhesions, fissures, erosions of glans and prepuce and involvement of the urethra are indications for surgical treatment. Surgery seems to be the only treatment that can relieve the symptoms of advanced disease. Modified circumcision, with total removal of inner preputial layer, definitively relieves phimosis without any recurrence. Meatotomy will not prevent the recurrence of meatal stenosis. Excision of the scleroatrophic tract and grafting of the glans base, coronal sulcus, and the end of the shaft give a complete relief of pain during erection and intercourse in circumcised patients with balanopreputial adhesions and restore the elasticity of the skin of penile shaft. These procedures have been shown to yield excellent functional results during a follow-up period of up to 4 years. BXO involving anterior urethra can be treated by 2-stage urethroplasty or substitution urethroplasty. The complete excision of the stricture and flap urethroplasty seems to be better than a 2-stage procedure. However, at the present time, it is not possible to say that surgery can completely resolve this chronic and progressive disease. Despite many reports in the literature of cases of BXO associated with squamous cell carcinoma, the etiologic relationship between the two conditions is uncertain.     

Development of a new metastatic human breast carcinoma xenograft line.

Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient''s tumour from which the xenograft line originated. Both the xenograft and the patient''s tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogen-responsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.     

Overview of fungal rhinosinusitis

The incidence of fungal rhinosinusitis has increased to such extent in recent years that fungal infection should be considered in all patients with chronic rhino sinusitis. In India though the disease was reported earlier only from northern regions of this country, nowadays the disease is increasingly diagnosed from other parts as well. The disease has been categorized with possible five types: acute necrothing (fulminant), chronic invasive, chronic granulomatous invasive, fungal hall (sinus mycetoma), allergic. The first three types are tissue-invasive and the last two are non-invasive fungal rhinosinusitis. However, the categorization is still controversial and open to discussion. Chronic fungal rhinosinusitis can occur in otherwise healthy host and Aspergillus flavus is the common etiological agent in Indian scenario. The pathophys iologic mechanism of the disease remains unclear. It may represent an allergic IgE response, a cell-mediated reaction, or a combination of two. Early diagnosis may prevent multiple surgical procedures and lead to effective treatment. Histopathology and radio-imaging techniques help to distinguish different types and delineate extension of disease process. Culture helps to identify the responsible etiological agent. The presence or absence oj precipitating antibody correlates well with disease progression or recovery. The most immediate need regarding management is to establish the respective roles of surgery and antifungal therapy. Non-invasive disease requires surgical debridement and sinus ventilation only, though, additional oral or local corticosterold therapy may be beneficial in allergie type. For invasive disease, the adjuvant medical therapy is recommended to prevent recurrence and further extension. Itraconazole has been found as an effective drug in such situation. Patients with acute neerotizing type require radical surgery and amphotericin B therapy.