Daily and photoperiodic 2- 125I-melatonin binding changes in the pars tuberalis of the Syrian hamster (Mesocricetus auratus): Effect of constant light exposure and pinealectomy

Abstract: Using quantitative autoradiography, 2¹²⁵I-melatonin binding was investigated throughout the light/dark cycle in the pars tuberalis (PT) of the pituitary of adult Syrian hamsters kept for 8 weeks either in long or short photoperiod (LP or SP, respectively). Melatonin receptor density in the PT displayed photoperiod dependent daily variations (maximal values in LP). Indeed, in LP, melatonin receptor density underwent strong daily variations with maximal values during the first half of the light period and minimal values at the end of the night. These variations depended on changes in the maximal binding (B_max) without differences in the dissociation constant (K_d). In contrast, PT melatonin receptor density was constant and at a very low level throughout the 1ight:dark cycle in SP exposed animals. Daily PT melatonin receptor density variations of LP exposed animals were abolished by pinealectomy or continuous light exposure. These results show clearly that both at the daily and at the seasonal level the regulation of PT melatonin receptors is strongly dependent on circulating melatonin concentrations in the Syrian hamster, but that other regulatory factors, yet unclarified, might also play a role.     

Evaluation of the genotoxic potential of glutaraldehyde

The cytotoxic and genotoxic effects of glutaraldehyde were studied in vitro in the human TK6 lymphoblast cell line and in primary cultures of rat hepatocytes. TK6 lymphoblasts were exposed to glutaraldehyde for 2 hr in serum-free GSH-free media. Cytotoxic effects were observed at concentrations as low as 10 microM with only 10% cell survival at 20 microM. Alkaline elution studies indicated that glutaraldehyde-induced DNA-protein crosslinking increased linearly over the concentration range from 0 to 25 microM. Glutaraldehyde-induced mutations were assessed at the thymidine kinase locus over the same concentration range and reached a plateau at 10 microM of about six times the background mutant frequency. At equivalent levels of DNA-protein crosslinks and cytolethality, glutaraldehyde was mutagenic at approximately a one-seventh lower concentration than the rodent nasal carcinogen formaldehyde (Craft et al.; Mutation Research 176:147-155, 1987). Glutaraldehyde induced a marginal increase in unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay, but only at the two highest concentrations of 50 and 100 microM, indicating the induction of some DNA excision-repair activity. These data demonstrate that glutaraldehyde exhibits DNA-reactive genotoxic activity that may involve, at least in part, DNA-protein crosslinking in these cell culture models. These findings suggest the need to examine the potential carcinogenic activity of glutaraldehyde in appropriate inhalation studies.     

The results of combined cataract extraction and trabeculectomy using separate incisions

A method of combined cataract extraction with posterior chamber intraocular lens and trabeculectomy using separate incisions was tested in 44 operations on 38 patients. The mean preoperative intraocular pressure (IOP) of 28.1 ± 11.7 (range 12 to 56) mmHg on maximum medication was lowered to 13.9 ± 3.4 (9 to 23) mmHg at one year, with half the eyes still requiring topical medication. The IOP was 40 mmHg or more preoperatively in eight eyes and 20 mmHg or more in only two patients at one year. There were no rises in IOP above 20 mmHg in the early postoperative period (days 1 and 2). Visual acuity was 6/9 or better in 27 and 6/12 in three eyes. There was an expulsive haemorrhage in one case, rupture of the posterior capsule in two eyes and a choroidal detachment in one eye, but no flat anterior chambers. The two-incision method allowed placement of an intraocular lens with good postoperative pressure control.     

Ca2+-activated K+ (KCa) channels are involved in the relaxations elicited by sildenafil in penile resistance arteries

The aim of the present study was to evaluate the role of K+ channels in the vasorelaxant effect of the phosphodiesterase 5 inhibitor, sildenafil, in isolated horse penile resistance arteries mounted in microvascular myographs. In phenylephrine-precontracted arteries, sildenafil elicited potent relaxations which were markedly reduced by raising extracellular K+, by the non-selective blocker of Ca2+-activated K+ channels (KCa), tetraethylammonium and by the blocker of large- and intermediate-conductance KCa channels, charybdotoxin. Sildenafil relaxant responses were also reduced by the selective inhibitor of large conductance KCa (BK(Ca)) channels iberiotoxin, but not by the blocker of small conductance KCa channels apamin. The inhibitor of the cGMP-dependent protein kinase (PKG), Rp-8-Br-PET-cGMPS, reduced the relaxations elicited by sildenafil but combined treatment with iberiotoxin and Rp-8-Br-PET-cGMPS did not further inhibit these relaxations, compared to the effect of either blocker alone. Iberiotoxin also shifted to the right the relaxations elicited by both the NO donor, S-nitrosoacetyl-D,L-penicillamine (SNAP) and the adenylate cyclase activator forskolin; treatment with both iberiotoxin and Rp-8-Br-PET-cGMPS did cause an additional inhibition. The present results demonstrate that the relaxant effect of sildenafil and NO in penile resistance arteries is due in part to activation of BK(Ca) channels through a PKG-dependent mechanism.     

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.     

Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum

We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound 1 reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA (2)-induced oedema in mouse paws. The flavone inhibited leukotriene B (4) formation in rat neutrophils and elastase release in human neutrophils, but did not reduce the expression of cyclooxygenase-2 (COX-2) in murine RAW 264.7 macrophages. These experimental results suggest that 1 may act through a direct inhibition of 5-LOX, without affecting the expression of COX-2.     

Tuberculosis of the large bowel

Summary Tuberculosis of the large bowel is relatively rare and is encountered more commonly in general hospitals than in santoria. Generally it involves the ileocecal region and often transforms it into a granuloma. Ileocecal tuberculosis often produces mechanical obstruction which requires a surgical operation. Surgical treatment consists of removal of the diseased segment of bowel and the regional nodes. In case resection is not possible, diversion of the fecal stream by exclusion of the diseased segment may be performed. Probably, aided by more antibiotic and chemotherapeutic medication, limited resection of the obstructing segment will suffice. Read at the meeting of the American Proctologic Society, Pittsburgh, Pennsylvania, June 21 to 24, 1961.