Analgesic effect of environmental noise: a possible stress response in rats

Environmental noise is a known stress, which induces alterations of various physiological responses in individuals exposed to it. Stress has been shown to cause changes in the perception of various sensations including pain and stress-induced analgesia has been observed following exposure to a diverse set of stimuli. To examine the algesic behavior of rats exposed to loud environmental noise, for long duration, we used an environment simulating chamber and conducted the tail flick test for the assessment of pain. The rats were divided into groups and subjected to loud noise for test sessions lasting 1 h, 2 h or 3 h in trials of 5 consecutive days. The noise was of two kinds--a continuous shrill noise (pure tone 92 dB & 98 dB) and an intermittent heavy artillery noise (white noise 102 dB). 15 min before and after each test session, tail flick latencies (TFL) were recorded at 5 min interval. The TFL recorded were normalised to an Index of Analgesia (IA) and the readings statistically analyzed using the F test (ANOVA), the significance being obtained by Tukey's test (at 5% level). The results revealed a significant increase in the TFL and the IA (P < 0.0001) in all the test groups demonstrating a significant analgesic response in rats subjected to noise stress. The analgesia was maximum immediately after noise exposure and declined with time. It was found to be directly related to the duration of exposure, the intensity and the characteristics of the noise with loud intermittent (white) noise and longer duration of exposure producing more analgesia.     

Canadian guidelines for economic evaluation of pharmaceuticals. Canadian Collaborative Workshop for Pharmacoeconomics

In 1994, Canada became the second country to release national guidelines for the economic evaluation of pharmaceuticals. The guidelines were developed over a period of 18 months through an elaborate process of broad consultation with a wide variety of relevant stakeholders. The intent of the guidelines is to provide guidance to doers and users of studies, by laying out the general 'state of the art' regarding methods, and by providing specific methodological advice on many matters. The aim is to improve the scientific quality and integrity of studies, and to enhance consistency and comparability across studies. This article presents the Canadian guidelines, both in summary and in detail. Because the techniques of economic evaluation are widely applicable beyond pharmaceuticals, the guidelines will be of interest to researchers and decision makers in all fields of healthcare. Because the methods are not country specific, the guidelines will be of interest to those in other countries as well as in Canada.     

Endoscopic carpal tunnel release: a single-portal technique

A safe single-portal technique for performing endoscopic carpal tunnel release is described. The procedure can be done using equipment already available in any standard operating room. Evaluation of 100 cases done by the author using this method has shown encouraging results.     

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats

Summary The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 g/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.Deceased February 13, 1979     

Etanidazole as a modulator of combined modality therapy in the rat 9l-gliosarcoma

The use of chemotherapy has led to improved treatment outcome for some pediatric patients with medulloblastoma. We have used a pre-radiation chemotherapy regimen consisting of vincristine and CDDP. The 9L gliosarcoma implanted intracranially and subcutaneously in the same animals was used as a preclinical model system to assess the efficacy of treatment combinations including: vincristine, CDDP, cyclo-phosphamide, etanidazole and radiation. The experimental endpoints were percent increase-in-lifespan, tumor growth delay and tumor cell survival. Both the tumor growth delay and percent increase-in-lifespan improved as the number of agents included in the chemotherapy regimen increased. so that the chemotherapy regimen including all four agents (ETA/VIN/CDDP/CTX) resulted in the greatest tumor growth delay (23.6 +/- 1.5 days) and the greatest increase-in-lifespan (35.8%). When radiation (20 Gray, single dose) was added to the treatment regimens the combinations of ETA/CTX/X-ray and ETA/VIN/CDDP/CTX/X-ray resulted in equivalent tumor growth delays (25.2 +/- 1.3 days and 25.8 +/- 1.7 days, respectively), while the greatest increase-in-lifespan (39.1%) was obtained with the five agent combination. The response of the 9L gliosarcoma to CDDP and cyclophosphamide over a dosage range was very similar to that of the murine FSaII fibrosarcoma. Our results indicate that etanidazole may be an effective chemosensitizer of combination chemotherapy and combined modality treatment regimens for brain tumors.     

Chlorinated hydrocarbon insecticide residues in tennessee honey and beeswax

Several samples of commercial grade honey collected from different parts of Tennessee during the summer of 1973 were analyzed for chlorinated hydrocarbon insecticide (CHI) residues. A Modified Mill's Procedure was used to cleanup the samples prior to gas Chromatographic analysis using electron capture (EC) detection. The presence of CHI residues was confirmed by analysis on three different columns of widely varying polarity. Most of the samples contained CHI residues at 0.01—0.30 parts per billion (ppb) level. Beeswax produced during the same season contained several times higher levels of the residue than the honey samples. Recoveries of CHI residues varied from 81–95 percent by the procedure employed.     

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.     

Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ. Absence of histological changes in the colon of rats treated with BDMC-A, shows that long term administration of BDMC-A is nontoxic to experimental animals. Our study suggest that BDMC-A may emerge as a potent anticarcinogenic agent against colon cancer. As both BDMC-A and curcumin are equipotent in inhibiting the DMH-induced colon tumor incidence and normalizing histological changes, it could be concluded that the terminal phenolic group and the conjugated double bonds in the central seven carbon change may be responsible for the beneficial effects.     

Type 1 diabetic mice are protected from acetaminophen hepatotoxicity.

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.