Opioid and GABA receptors involved in mediation and modulation of tonic and stimulus-evoked inhibition of a spinal reflex in the decerebrated and spinalized rabbit

The purposes of this study were to investigate: (i) the identity of the opioid peptide(s) mediating tonic and stimulus-evoked inhibition of the sural-medial gastrocnemius reflex of the decerebrated, spinalized rabbit and (ii) the modulation of these processes by endogenous GABA. The selective delta receptor antagonist naltrindole (100 nmol kg(-1) i.v.), the GABA(A) blocker bicuculline (300 nmol intrathecal, i.th.), and the GABA(B) antagonist CGP 35348 (1 micromol i.th.) increased gastrocnemius reflexes to 150-160% of pre-drug values, whereas a sub-maximal dose of naloxone (30 nmol kg(-1) i.v.) augmented reflexes to >500% of controls. Kelatorphan, an inhibitor of enkephalin metabolism (2 micromol i.th.), depressed gastrocnemius responses by 50% and potentiated the inhibitory effects of methionine enkephalin.Repetitive electrical stimulation of the superficial or common peroneal nerves inhibited reflexes for 15-20 min. This effect was significantly reduced by naltrindole and CGP 35348. It was not reduced by a low dose (30 nmol kg(-1) i.v.) of naloxone or by bicuculline. When naloxone and naltrindole were combined at 30 nmol kg(-1) each, stimulus-evoked inhibition was blocked. Given after bicuculline, naloxone at 100 nmol kg(-1) i.v. abolished peroneal-evoked inhibition, but a dose of 300 nmol kg(-1) was required to produce the same effect after CGP 35348. Kelatorphan augmented the depth and duration of inhibition evoked by peroneal nerve stimulation. These data are consistent with the involvement of enkephalin-like peptides in tonic and stimulus-evoked inhibition of the sural-gastrocnemius reflex. Tonic inhibition in rabbit spinal cord is dominated by opioids acting through mu receptors, whereas co-activation of delta, mu and GABA(B) receptors mediates stimulus-evoked inhibition. It is possible that GABA(B) receptors inhibit the release of spinal opioids while simultaneously supporting their actions at post-synaptic targets.     

Sequential bilateral total knee arthroplasty under 1 anesthetic in patients > or = 75 years old: complications and functional outcomes

The objectives of this study were to determine the perioperative surgical and medical risks associated with sequential bilateral total knee arthroplasty (TKA) in patients > or = 75 years old and to assess their functional status and overall level of satisfaction at follow-up. Study participants were 82 consecutive patients > or = 75 years old who underwent a sequential bilateral TKA and 82 matched patients who underwent a unilateral TKA. There were 46 postoperative complications in the bilateral TKA group compared with 27 in the unilateral TKA group (P = .003). Postoperative cardiovascular complications were significantly greater in the sequential bilateral TKA group and were associated significantly with preoperative cardiovascular comorbidity. The mean Modified Hospital for Special Surgery knee score was rated as good (mean, 63.5 out of 80), and 95% of patients rated their knees as excellent or good at follow-up. Sequential bilateral TKA in patients > or =75 years old results in high patient satisfaction and good functional status at follow-up; however, there is an increased risk of cardiovascular complications during the postoperative period in bilateral sequential TKA patients when compared with a matched cohort of unilateral TKA patients.     

Fumonisin toxicity in a transgenic mouse model lacking the mdr1a/1b P-glycoprotein genes

The toxicity of fumonisin B(1) (FB(1)) was investigated in male mdr1a/1b double knockout (MDRK) mice, lacking the drug-transporting P-glycoproteins. These transgenic animals are deficient in their blood:brain barrier and accumulate different drugs in brain and other tissues. The MDRK and their wild-type counterparts, FVB mice, were injected subcutaneously with 2.25 mg/kg per day of FB(1) for 5 days and sampled one day after the last treatment in a protocol that has resulted in marked hepatic and renal damage in other strains. FB(1) caused liver enlargement in both FVB and MDRK. Hematological parameters were not affected in either strain. Plasma levels of alanine aminotransferase and aspartate aminotransferase, measures of liver damage, were increased by FB(1) in both FVB and MDRK mice. Histopathological evaluation of liver corroborated this finding. Kidney lesions were induced by FB(1) in both types of mice. Concentrations of free sphingosine and sphinganine increased in liver and kidney of both strains after the FB(1) treatment, although the increase in liver sphingoid bases was half as much in MDRK as compared to FVB. The levels of sphinganine-containing complex sphingolipids were increased in kidney. The levels of sphingosine-containing complex sphingolipids in kidney were unaffected by FB(1) treatment but were significantly lower in control MDRK than in FVB mice. The levels of neurotransmitters and their metabolites were similarly affected in both strains by FB(1), suggesting no influence of disrupted blood:brain barrier on FB(1)-induced neurotoxicity. In both strains, the liver mRNA for tumor necrosis factor alpha was increased; however, the increase was statistically significant only in FVB. It was apparent that mice deficient in P-glycoprotein do not exhibit greater sensitivity to FB(1), the cellular or brain transport of FB(1) appears to be independent of this multidrug transporting system.     

Zinc therapy in Indian childhood cirrhosis

Fifty five histopathologically proved cases of Indian childhood cirrhosis (ICC) were studied for the effect of oral zinc oxide/zinc sulphate therapy both in doses of 120 mg/day. Twenty six patients were given zinc oxide, 19 were given zinc sulphate and 10 cases served as control. Serum zinc was estimated by atomic absorption spectrophotometer (ASS). Serum zinc was low in all the stages of ICC and was directly related to the severity of the disease. Serum zinc was 72±11μg/dl in stage I; 65±14μg/dl in stage II; 57±18 μg/dl in stage III compared with 123±23μg/dl in normal children. Inspite of oral zinc therapy clinical condition and liver histopathology advanced in all patients and they expired due to hepatic coma. It is concluded that hypozincemia in ICC is a nonspecific finding and zinc therapy has no role in its management. This study was carried out by research grant from Medical Research Center, Bombay Hospital Trust, Bombay—20.     

Allergy diagnosis by Pharmacia Cap System

From September 1995 to September 1998, sera from 959 suspected allergy patients have been tested by the new Pharmacia Cap System. Of these, 80 per cent were diagnosed to suffer from some allergy while 20 per cent reacted negative. It was found that the CAP system gave accurate and clear cut results to the satisfaction of the patient and referring physician.     

Ectodermal dysplasia

Summary Five children with ectodermal dysplasia are reported; three were of the anhydrotic variety. Clinical, radiological and histopathological features are commented upon. From the Pediatric Unit, R.N.T. Medical College, Udaipur, Rajasthan.     

Behcet’s syndrome

Two cases of Behcet’s Syndrome are being reported. One patient had hemoptysis and pulmonary lesions.