Evaluation of insulin resistance during inhibition of endogenous insulin and glucagon secretion by somatostatin in non-obese subjects with impaired glucose tolerance

Summary Insulin resistance was studied in seven non-obese male subjects with impaired glucose tolerance and four healthy, age and body-weight matched male control subjects by means of a continuous intravenous infusion of somatostatin, glucose and insulin over 150 min. Glucose tolerance was evaluated by means of a 2-h glucose infusion test. Endogenous insulin (C-peptide), growth hormone, and glucagon secretion were suppressed by somatostatin in both groups. Steady-state plasma insulin and glucose levels were achieved between 90–135 min. Since similar steady-state levels of exogenous insulin were achieved, the resulting steady-state plasma glucose level provided a direct estimate of the ability of insulin to dispose of the infused glucose. The glucose levels were higher in subjects with impaired glucose tolerance with values of 14.6 ± 1.8 mmol/1 compared with 5.1 ± 1.2 mmol/1 in control subjects (p < 0.01), thus indicating insulin resistance. There was a direct correlation between the steady-state plasma glucose level and glucose tolerance suggesting that the degree of glucose intolerance is proportional to the degree of insulin resistance. These results revealed that decreased insulin sensitivity is found in non-obese subjects with impaired glucose tolerance.     

Rimcazole (BW234U) in the maintenance treatment of outpatients with schizophrenia

Rimcazole (BW234U), a substituted carbazole compound, has been reported to be effective in treating acutely ill schizophrenic patients without significant extrapyramidal side effects. A two-phase study was done to assess the efficacy and safety of rimcazole in the maintenance treatment of schizophrenia. Study I was a double-blind comparison of rimcazole (50–300 mg daily) with haloperidol (5–30 mg daily) with ten stable schizophrenic outpatients. Three of six patients relapsed on rimcazole, while there were no relapses on haloperidol. One patient dropped out of each group. Extrapyramidal side effects were minimal in the rimcazole group, and two patients with tardive dyskinesia showed marked improvement in AIMS Scores. Study II was an open label trial of rimcazole using a higher maximum dose of 450 mg daily in seven schizophrenic outpatients. Four of the seven patients relapsed, at a mean of 7 weeks, one dropped out, and two patients remained stable. While the drug was generally well tolerated, both of the nonrelapsing patients developed transient elevations in liver transaminases. The small sample size in these studies prevents definitive conclusions to be drawn. There may be subgroups of schizophrenic patients who can be successfully maintained on rimcazole with less morbidity than from standard neuroleptic drugs.     

Cholinergic Innervation of Fetal Neocortical Transplants Is Increased after Neutralization of Myelin-Associated Neurite Growth Inhibitors

Fetal neocortical transplants placed into adult neocortical sensorimotor aspiration lesions are known to receive afferent input from the adult host rat brain. As this input is less dense than normal, the present study was designed to investigate whether neutralization of myelin-associated neurite growth inhibitors NI-35/250 might promote host derived cholinergic innervation of fetal neocortical transplants. Adult rats received unilateral sensorimotor cortical aspiration lesions, and block grafts from embryonic day 14–15 neocortical tissue were placed immediately into the lesion cavities. Mouse hybridoma cells secreting either the monoclonal antibody IN-1, which blocks neurite growth inhibitors NI-35/250, or a control antibody or medium without cells were applied in millipore filter capsules directly over the fetal graft tissue. The brains were processed 12 weeks later for the visualization of acetylcholinesterase-positive, presumptive cholinergic fibers. We found an enhancement in the cholinergic innervation of fetal grafts in the recipients treated with the antibody IN-1 both in terms of fibers growing into the graft and of density within the center of the grafts. These results indicate that myelin-associated neurite growth inhibitors are involved in the development of host–transplant connectivity in the adult brain.     

Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst_2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst_2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst_2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst_2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst_2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing μ-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst_2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or δ-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.     

Surgical and Anatomic Parameters Influencing Femoropatellar Pain in Total Knee Arthroplasty

Background: Femoropatellar pain occurs in up to 27% of patients after total knee arthroplasty. This complication may at least be partly related to postoperative malalignment and anatomic variations. Patients and Methods: In this study, 44 patients (eight male, 36 female) with an unconstrained knee arthroplasty (Genesis) without retropatellar resurfacing were evaluated over a follow-up of 40 (7-71) months. The patients' mean age at surgery was 69.3 (24-86) years. The Turba score was used for evaluation of the outcome. This score had been especially designed for femoropatellar knee pain. The type of patella (Wiberb), the patella shift, the patella tilt (Laurin et al), the patella height, the congruence angle (Merchant et al), and the lateral angle between femur and tibia were evaluated by X-ray examination. Results: Pain was found to correlate significantly with the subjective part of the Turba score. This result has to be expected as pain itself is a subjective criterion. But pain is not always accompanied by poor results in the objective part of the score. Contrary to the literature, the result of this study could not confirm that the parameters patela shift, congruence angle, patella height, lateral patella tilt, lateral femorotibial angle, patella type, and range of motion significantly correlate with anterior knee pain. Conclusion: For none of the investigated anatomic and surgical parameter, a connection with anterior knee pain after knee arthroplasty could be confirmed.     

Role of the mitochondrial bc1-complex in the cytotoxic action of diethylstilbestrol-diphosphate toward prostatic carcinoma cells

In previous work (P. Schulz et al., Cancer Res., 48: 2867-2870, 1988) we have demonstrated that diethylstilbestrol (DES), DES-monophosphate, and DES-diphosphate (DESDP) are generally cytotoxic at concentrations attained in patients' sera during therapeutic DESDP infusions for progressed carcinoma of the prostate. We have extended this work and addressed two questions: (a) Is DESDP itself a completely nontoxic prodrug which has to be transformed into the active species DES by a phosphatase? (b) Which metabolic or regulatory mechanism in a cell is the target of DES action? Using cell cultures in phosphatase-depleted media we could provide evidence that DESDP exerts cytotoxic activity only after conversion to DES. Oxygen electrode experiments and difference spectra with intact mitochondria demonstrated that DES did not act as an uncoupler, but inhibited electron flow from ubiquinone to cytochrome c1. Phenomena previously observed in DES-treated cells could be explained by distortion of the energy metabolism.     

Genetic studies in etiologically different chronic liver diseases

In 198 patients with chronic liver diseases of different etiology 16 genetic feature systems were investigated (blood groups, erythrocytic enzymes, immunoglobulin allotypes, proteins). In comparison to a representative normal population significant differences of the frequency of the distribution of phenotypes of various systems were found. In these cases is remarkable that association between genetic markers and hepatopathies were above all proved in their classification according to etiopathogenetic criteria. We evaluate our findings as a reference to the importance of genetic factors in the development of chronic liver diseases.