Activation of phospholipase C and guanylyl cyclase by endothelins in human trabecular meshwork cells

PURPOSE: To characterize effects of endothelins on activities of phospholipase C (PLC) and nucleotide cyclases in human trabecular meshwork (TM) cells. METHODS: Cultured simian virus 40-transformed human TM (HTM-3) or non-transformed (HTM-16) cells were used. Changes in the PLC activity were determined by assaying the production of [3H] inositol phosphates. Accumulation of cyclic GMP or cyclic AMP in cell lysate was measured by radioimmunoassay. RESULTS: Endothelin-1 (ET-1; 1 microM) stimulated PLC in HTM-16 cells, but Sarafotoxin S6c (SRTX), an ET(B) receptor subtype-selective agonist (1 microM), did not. Similar results were obtained in HTM-3 cells: ET-1, but not ET-3 or SRTX, activated PLC in a dose-dependent manner, with a calculated EC50 of 646 pM. The peptide also stimulated the accumulation of cGMP in a concentration-dependent manner with an EC50 of 37.2 pM. ET-3 or SRTX was not effective except at much higher concentrations. Both the PLC and guanylyl cyclase stimulation induced by ET-1 (10 nM) were completely inhibited by pretreating the cells with BQ-123 (<10 microM), an ET(A) receptor selective antagonist, but not by BQ-788 (10 microM), an ET(B) receptor subtype-specific antagonist. Neither ET-1 nor ET-3 stimulated adenylyl cyclase activity in HTM-3 cells at concentration as high as 1 microM. CONCLUSION: ET-1 activates PLC and guanylyl cyclase in TM cells. Potency profiles of ET receptor agonists and antagonists suggest that the ET(A) receptor subtype is involved in both actions of ET-1. The effects of the ET peptides in TM cells are interesting and could be part of the mechanism of their IOP-lowering effect.     

Propofol and electroconvulsive therapy in a patient at risk from acute intermittent porphyria

Evidence for the involvement of the cranial arterial system in migraine is plentiful, but it is unclear whether the cranial venous system may be involved in the mechanism of migraine pain. Venules are the preferentially involved vessels in the neurogenic inflammation animal model of migraine. The cranial and cerebral veins and sinuses are pain sensitive and receive sensory innervation from the trigeminal nerve. If the veins are involved in migraine pathogenesis, a venous dilatation would presumably be painful. The effect of a short lasting cranial venous dilatation, induced by applying pressure on the internal jugular veins (Queckenstedt's manoeuvre), was therefore compared with a placebo procedure, consisting of an equal pressure applied on to the lateral aspect of the neck. In each procedure pressure was applied for 10 seconds. The study used a single blind, randomised, cross over design, and 20 patients with an acute attack of migraine without aura participated. After each procedure, headache intensity was rated on a standardised five point scale. After Queckenstedt's manoeuvre 40% of the patients reported no change in headache intensity, 25% a worsening, and 35% an improvement of their headache. No significant difference between the headache intensity ratings during Queckenstedt's manoeuvre and the placebo manoeuvre was found (p=0.22). The findings make it unlikely that the cephalic venous system is of major importance in migraine pain mechanisms and, therefore, also less likely that neurogenic inflammation plays a significant part in humans during attacks of migraine without aura.     

Disseminated candidiasis (moniliasis) in a dog. A case report

A case of systemic candidiasis (Candida albicans) in a 1 1/2 year old dog is reported. Clinically, the first manifestation was enlargement of a superficial inguinal lymph node. Later several peripheral lymph nodes were affected and a fistulous opening appeared, communicating with an inflammatory process in the right humerus. Necropsy revealed gross lesions in the kidneys, pancreas and multiple lymph nodes. In addition, microscopic lesions were observed in the myocardium and the bone marrow of the right humerus. The lesions, which contained large fungal colonies, were mainly granulomatous with numerous multinuclear giant and epitheloid cells, but necrosis and suppuration were also evident. The site of invasion is not known. However, a previous perianal and abdominal dermatitis, which was treated locally with antibiotics and corticoids, could possibly have been a mycotic infection.     

Spironolactone and acute mountain sickness

Thirteen adults trekking in Nepal in 1974 to altitudes between 4,300 m and 5,500 m remained free from acute mountain sickness while taking spironolactone as a prophylactic measure. Two years previously five of these adults trekking at similar altitudes, but without treatment, had suffered from acute mountain sickness. The regime used was spironolactone in a dosage of 25 mg three times a day for two days preceding and during the periods spent at altitudes above 3,000 m.     

Effect of substance P on proximal tubular reabsorption in the rat

Micropuncture and clearance techniques were used simultaneously to determine the effect of substance P on proximal tubular and overall renal function in anesthetized rats. This polypeptide, infused in saline at 50 pg/min into the abdominal aorta above the renal arteries, produced increases in urine flow, 2.7-3.7 mul/min.g kidney wt (P is less than 0.005); urinary sodium concentration, 32-61 meq/liter (P is less than 0.01); and sodium excretion, 89-223 neq/min (P is less than 0.005). Tubular fluid to plasma inulin concentration ratio measured in the last accessible proximal convolution fell from 2.21 to 1.80 (P is less than 0.001), and thus fractional reabsorption was reduced from 54 to 44% (P is less than 0.001). Absolute reabsorption by the proximal convoluted tubule was also reduced 15.5-12.5 nl/min (P is less than 0.025). In a control series of animals, saline alone infused at the same rate did not produce any statistically significant changes in the measured parameters over the same time period. The intrerenal mechanism responsible for the reduction in proximal reabsorption appears to be a tubular one since no consistent or significant changes were observed in kidney or single nephron glomerular filtration rate, renal plasma flow, or intrarenal hydrostatic pressures. No evidence was found to indicate redistribution of filtration rate, or plasma flow, or a reduction in filtration fraction.     

Digital processing of chest radiographs

Plain film radiography is the most common imaging method used in the diagnosis of diseases of the heart and lungs. Despite this, little attention has been given to the possible advantages of capturing and subsequently processing such images digitally. This paper describes the application of digital image processing techniques to chest radiographs. The use of different image enhancement techniques is discussed and their clinical value in diagnosis is illustrated. Attention is given to techniques that aid the clinician in visualizing detail in low contrast regions of the image and detecting lesions such as pneumothoraces. These techniques benefit the patient by reducing the X-ray dose, as well as increasing the information that may be extracted from the image.