ABSTRACT
OBJECTIVE: We aim to describe the supraclavicular nerve's vascular entrapment by the external jugular vein as an unreported anatomical finding. CASE DESCRIPTION: In a routine cadaveric dissection, the superficial emergence of the first division of the left supraclavicular nerve emerged along a duct formed through the external jugular vein. No other vascular or neural anatomical abnormalities were found in the surrounding structures. CONCLUSION: This unreported vascular entrapment of the supraclavicular nerve by the external jugular may harbour clinical implications for surgical and endovascular procedures on the external jugular vein and in refractory thoracic and scapular waist pain.
Subject(s)
Jugular Veins , Nerve Compression Syndromes , Dissection , Humans , Jugular Veins/diagnostic imaging , Subclavian Vein/diagnostic imagingABSTRACT
A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.
Subject(s)
Alkaloids/chemical synthesis , Indoles/chemistry , Invertebrates/chemistry , Alkaloids/chemistry , Animals , Magnetic Resonance Spectroscopy , Mass Spectrometry/methods , Molecular StructureABSTRACT
A series of tryptamine analogues has been prepared and tested for their 5-HT1 receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate antihypertensive and bradycardic response in anaesthetized spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at the beta-position of the side-chain of the tryptamines significantly increased the mean resting arterial blood pressure (MAP) in pithed rats and also produced contraction of the canine basilar artery in a dose-dependent fashion. Structure-activity relationships (SAR) suggest that the 5-alkoxy group is an important pharmacophore in the production of the antihypertensive effect and that the introduction of a hydroxymethylene group on the side-chain, instead of the carbomethoxy group, changed the receptor affinity profile.
Subject(s)
5-Methoxytryptamine/analogs & derivatives , 5-Methoxytryptamine/pharmacology , Antihypertensive Agents/pharmacology , Serotonin Receptor Agonists/pharmacology , 5-Methoxytryptamine/chemical synthesis , Animals , Antihypertensive Agents/chemical synthesis , Basilar Artery/drug effects , Basilar Artery/physiology , Blood Pressure/drug effects , Decerebrate State , Dogs , Female , Heart Rate/drug effects , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Rats , Rats, Inbred SHR , Rats, Wistar , Receptor, Serotonin, 5-HT1D , Receptors, Serotonin/drug effects , Receptors, Serotonin, 5-HT1 , Serotonin Receptor Agonists/chemical synthesis , Structure-Activity RelationshipABSTRACT
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease.
Subject(s)
Antigens, Differentiation/genetics , Chromosomes, Human, Pair 2/genetics , Diabetes Mellitus, Type 1/genetics , Genetic Linkage , Immunoconjugates , Abatacept , Antigens, CD , CTLA-4 Antigen , Case-Control Studies , Exons/genetics , Genetic Predisposition to Disease , Graves Disease/genetics , Humans , Nuclear Family , Point Mutation , Polymorphism, GeneticABSTRACT
In this paper relevant studies are summarized regarding the use of acarbose as an adjunct to insulin in the treatment of type I diabetes. It is concluded that this approach may contribute to a reduction of postprandial blood glucose excursions and a smoothening of daily blood glucose profiles, an improvement of metabolic control as expressed by glycosylate haemoglobin values and a reduction of insulin requirements. Long-term studies are, however, necessary before one can conclude that addition of acarbose to the therapeutic regimen in type I diabetic subjects is of longstanding value.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Glycoside Hydrolase Inhibitors , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Trisaccharides/therapeutic use , Acarbose , Adult , Blood Glucose/drug effects , Blood Glucose/metabolism , Child , Clinical Trials as Topic , Diabetes Mellitus, Type 1/blood , Drug Therapy, Combination , Female , Humans , Male , Multicenter Studies as TopicABSTRACT
SMS 201-995 is a new somatostatin analog which is 10-60 times more potent and specific than somatostatin as an inhibitor of GH and insulin release. The aim of this study was to assess its value as an adjunct to insulin therapy in insulin-dependent diabetic- (IDD) patients. Six IDD patients were studied. Their average insulin doses ranged from 22-46 U/day, and hemoglobin A1c levels varied between 6.5-11.5%. Two patients had background retinopathy and mild sensorimotor neuropathy. After 12 h of glucemic stabilization, the patients were kept normoglycemic by connecting them to the Biostator-GCIIS. The study entailed two parts in random order, in which standardised mixed meals were administered at 0800, 1400, and 2000 h with or without sc bolus injections of 50 micrograms SMS 201-995 immediately before meal ingestion. Plasma free insulin, C-peptide, GH, and glucagon were measured by RIA. Postprandial hyperglycemia was significantly diminished by SMS 201-995 after breakfast, lunch, and dinner. Insulin requirements, both total and 2-h postprandially, decreased significantly with a parallel reduction in free insulin levels. Postprandial glucagon levels also significantly decreased, but GH profiles were similar. In conclusion, the somatostatin analog SMS 201-995 has a potential value as an adjunct to insulin in the management of IDD patients.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/therapeutic use , Somatostatin/analogs & derivatives , Adult , Blood Glucose/metabolism , C-Peptide/blood , Female , Growth Hormone/blood , Humans , Insulin/blood , Male , Middle Aged , Monitoring, Physiologic , Octreotide , Somatostatin/therapeutic useABSTRACT
[125I]Insulin binding has been studied with cultured cells from an insulin-resistant patient with the Rabson-Mendenhall syndrome. Previously, this patient has been demonstrated to have decreased insulin binding to circulating blood cells. Similarly, [125I]insulin binding to cultured lymphocytes and cultured fibroblasts was markedly decreased. Whereas the decrease in [125I]insulin binding to cultured lymphocytes appeared to result from a decrease in receptor number in cultured lymphocytes, there appeared to be a reduction in the affinity of [125I]insulin binding to cultured fibroblasts. This discrepancy between the observations with the two cell types is a general phenomenon which has been described in patients with a variety of syndromes of extreme insulin resistance. It is possible that the interpretation of the studies with the fibroblasts is complicated by the confounding influence of receptors for insulin-like growth factors on the surface of those cells. If the number of insulin receptors is sufficiently reduced on fibroblasts from the patient with extreme insulin resistance, then the low level of residual [125I]insulin binding may involve primarily receptors for insulin-like growth factors, which bind insulin with relatively low affinity.
