Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Inhibin and age in men

OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.     

Surgical management of trismus due to Oral Submucous Fibrosis — Lysis of fibrotic bands with the KTP-532 Laser

Oral Submucous Fibrosis is an insidious, chronic disease affecting the oral cavity, sometimes the pharynx and rarely the tongue. 15 patients with Oral Submucous Fibrosis presenting with severe trismus were treated with lysis of the fibrotic bands with a KTP-532 Laser and adjunctive treatment with excellent results over a 12 month follow-up period.     

Secondary pharyngeal tuberculosis

Secondary tuberculosis of pharynx is a rare condition as pharynx is not a common site for clinically manifest tuberculosis. A rare and unusual case of secondary oropharyngeal tuberculosis in a 40 years male patient, who presented with an ulceroproliferative lesion of oropharynx extending to nasopharynx and laryngopharynx is being reported.     

Long term performance of silicone insulated and polyurethane insulated cardiac pacing leads.

The long term performance of various pacing leads in use for at least one year is reported from one centre. Between January 1975 and December 1990, 1056 cardiac pacing leads were implanted in 881 patients (mean age 57 +/- 13 years). Eight hundred and three leads were silicone insulated (SI) and 253 leads were polyurethane insulated (PUI). Leads from different manufacturers were used (Medtronic, CPI, Telectronics). The average duration of follow up was 56.6 +/- 77 months (range 12-221 months) for SI and 47.1 +/- 24 months (range 12-99 months) for PUI leads. Overall lead failure occurred more often in the PUI group (n = 46, 18.2%) compared to SI group (n = 93, 11.3%, p < 0.025). Majority of lead failures occurred in the first 36 months after implantation. In particular, Medtronic models 6971, 6972 (urethane) and 6901 (silicone) showed higher rate of complications (25.5%, 26.3% and 44.5% respectively).