Activation of phospholipases A1 and A2 in heart, liver, and blood during endotoxin shock

The effects of endotoxin shock on the activities of phospholipases A1 and A2 were studied in canine heart sarcolemma, liver plasma membrane, and blood serum. Results obtained from control dogs indicate that phospholipases A1 and A2 were equally active in cardiac sarcolemma. In liver plasma membrane the activity of phospholipase A1 was twice that of phospholipase A2, while in blood serum phospholipase A1 activity was only half that of phospholipase A2. Results obtained 4 hr after endotoxin administration (0.5 mg/kg, iv) demonstrate that phospholipase A1 activities were activated by 117% in cardiac sarcolemma, 188% in liver plasma membrane, and 150% in blood serum, while phospholipases A2 activities were stimulated by 71% in cardiac sarcolemma, 175% in liver plasma membrane, and 31% in blood serum. The in vitro incubation of all three enzyme preparations from control dogs with endotoxin (5-15 micrograms/0.5 ml) stimulated both phospholipase A1 and A2 activities and the stimulation was concentration dependent. These data suggest that endotoxin may have a direct stimulatory effect on phospholipases A1 and A2 activities in the cell membranes of heart and liver, and also in blood serum. Since phospholipases A play an important role in the regulation of membrane structure and function, the observed activation of phospholipases A1 and A2 may have a physiological significance in the pathogenesis of cellular dysfunction in endotoxin shock.     

Analysis of two types of cone bipolar cells in the retina of a New World monkey, the marmoset, Callithrix jacchus.

Two types of cone bipolar cells, the blue cone bipolar cell and the diffuse bipolar cell (DB3), were labelled immunohistochemically and investigated in the retina of a New World monkey, the marmoset. Blue cone bipolar cells were labelled with an antiserum against cholecystokinin. Short-wavelength-sensitive (SWS) cones were labelled with an antiserum against the SWS cone opsin. The DB3 cells were labelled with antibodies to calbindin. Blue cone bipolar cells in marmoset do not form a regular mosaic but instead follow the random distribution of the SWS cones. Nevertheless, the SWS cone to blue cone bipolar cell connectivity in marmoset is very similar to that previously described for macaque. In contrast to the blue cone bipolar cells, the DB3 cells form a regular mosaic. The synaptic connectivity of DB3 cells in the inner plexiform layer was analyzed. They make output synapses onto ganglion cells and amacrine cells, and gap junctions with each other. Our results provide further evidence for the existence of parallel bipolar cell pathways in the primate retina and support the view that the retinae of Old World and New World primates have common neuronal connectivity. The random distribution of SWS cones and blue cone bipolar cells is an exception to the general rule of a regular mosaic distribution of cell populations in the retina.     

Midget and parasol ganglion cells of the primate retina express the alpha1 subunit of the glycine receptor

Glycine is a major inhibitory neurotransmitter in the mammalian retina and has been shown to influence the responses of ganglion cells. Midget and parasol ganglion cells serve distinct physiological roles in the primate retina and show differences in their response characteristics to light stimuli. In the present study, we addressed the question of whether the expression of glycine receptors differs in midget and parasol ganglion cells. Ganglion cells in the retinae of marmoset and macaque monkeys were injected with Neurobiotin in a live in vitro retinal whole-mount preparation. Retinal pieces were then processed with an antibody against the alpha1 subunit of the glycine receptor. Strong punctate immunoreactivity indicative of synaptic localization is present in the ON and OFF sublamina of the inner plexiform layer. Many of the immunoreactive puncta coincide with the dendrites of both midget and parasol ganglion cells. Immunoreactive puncta are present on distal and proximal dendrites of ON and OFF cells. These results suggest that ON and OFF midget and parasol cells do not differ with respect to the distribution of the alpha1 subunit of the glycine receptor.     

Factors influencing the acceptability and prolonged use of oral contraceptives.

The prospect of increasing the incidence of continued oral contraceptive (OC) users led to a planned study in which 100 women were given OCs for 1 year. Follow up occurred monthly for the first 3 months and was thereafter 3-monthly. Patients obtaining special attention could continue the pills for a longer duration and had minimum medical problems compared with those where individual attention was lacking. The difference lay presumably in prompt attention towards any trouble and the correct selection of pills. The survey indicates that the success of OCs depends on good educational status of the patients, special individual attention by the doctor, proper appraisal for the correct pill regimen, and frequent follow-up visits. Prompt discovery and treatment of any trouble can prevent disappointment and disillusionment with this method of contraception.     

Efficacy,safety, and tolerability of microsphere adapalene vs. conventional adapalene for acne vulgaris

Background The present study was undertaken to compare the efficacy, safety and tolerability of a new microsphere adapalene formulation and conventional adapalene in adult patients with mild to moderate acne vulgaris. Materials and Methods This prospective, randomized, assessor‐blind, multi‐centric (3 centres) comparative, post‐marketing phase IV study was undertaken in 175 patients with mild to moderate acne after approval by respective Institutional review boards. Patients fulfilling selection criteria were randomly assigned to either microsphere adapalene gel or conventional adapalene gel both once daily in the evening for 12 weeks after obtaining their informed consent. Efficacy variables included success rate and percent lesion reduction from baseline. Safety and tolerability was assessed on the basis of physical examination and monitoring of treatment–emergent adverse events. Results Of the 175 patients (88 in microsphere and 87 in conventional) 21 were lost to follow‐up and considered drop‐outs. There was a significant decrease (P < 0.05) in mean inflammatory and non‐inflammatory lesion and total lesion counts from 1st week onwards in both groups. A significantly lower number of microsphere treated patients (50%) reported a side effect (P < 0.05) as compared to 71.3% in conventional users. A highly significant decrease was observed in dryness and erythema (P < 0.01) in microsphere group compared to conventional. Eight patients in conventional group discontinued therapy due to severe irritation as compared to none in microsphere adapalene group. Comment Therapy with microsphere adapalene provided a better tolerability with minimal irritation compared to conventional adapalene, without compromising efficacy and could be a better therapeutic option for acne.     

Vitiligo patients from India (Mumbai) show differences in clinical,demographic and autoantibody profiles compared to patients in western countries

Background Vitiligo is a common, idiopathic skin disorder characterized by depigmented skin due to the loss of cutaneous melanocytes. Several studies have reported the clinical and demographic characteristics of Indian vitiligo patients, however, none has characterized their antibody profiles. Objective To establish the clinical, demographic and serological details of a population of vitiligo patients from Mumbai, India, and to evaluate the data for any associations between clinical presentations and the occurrence of antibody responses. Methods Vitiligo patients (n = 79) were recruited to the study and their clinical and demographic details recorded. Serum antibodies, including those against melanocyte‐specific antigens, thyroid antigens and keratinocytes, were evaluated. Results The prevalence of vitiligo was independent of sex, and non‐segmental vitiligo was the most common form of the disease occurring in 65% of the patients. Patients with segmental vitiligo (mean age = 14.4 ± 4.6 years) presented at a younger age than those with non‐segmental disease (mean age = 32.5 ± 17.8 years). Personal and family histories of other autoimmune diseases occurred in 3% and 8% of patients, respectively. Antibodies were detected against tyrosinase, tyrosine hydroxylase, thyroid peroxidase, thyroglobulin and keratinocytes at frequencies of 11%, 22%, 18%, 24% and 27%, respectively. Overall, antibodies were more common in patients with non‐segmental vitiligo (50–67%) than in those with segmental disease (0–17%), and were detected more frequently in patients with shorter disease durations (<10 years). Conclusion Our study provides novel information relative to the clinical details, demographic features and serological parameters of a population of vitiligo patients from Mumbai, India. Important distinctions from similar surveys conducted in European patients were evident such as an infrequency of family history, a low prevalence of clinical autoimmune disease, and an absence of particular antibody specificities. These differences may have a bearing on the pathogenesis and course of the disease in Indian patients.     

“Pseudo” Nomenclature in Dermatology: What's in a Name?

In the bewildering array of scientific nomenclature in the medical field, it is important to use correct terminology, know their aberrations and the reason behind a specific terminology. This paper is an attempt towards compiling all the pseudo-nomenclatures coined in dermatology, in order to make it easier to retain and recollect these pseudo names, signs, morphology, diseases, and conditions. It is also imperative to know the true entities that these pseudo names masquerade as, so as to understand the explanation for assigning the term ‘pseudo’ to these conditions. A total of 52 pseudo-terms have been compiled here in reference to dermatology. Most of these pseudo-nomenclatures were coined due to some clinical or histopathological resemblance to the true conditions, while some were premature conclusions drawn from a flawed understanding of the basic nature of the condition. Clear understanding of each of these terms and the explanation behind them being pseudo will enable a dermatologist to avoid misdiagnosis and needless confusion.     

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.     

Retinal function and PKC alpha expression after focal laser photocoagulation

Purpose

To examine the effects of focal laser photocoagulation on general and local retinal function and to relate electrophysiological findings with changes in protein kinase C (PKC) alpha expression.

Methods

Twelve rabbits were treated with 70 spots of laser photocoagulation in the central cone-rich retina. The operated eyes were investigated with electroretinography (full-field ERG and multifocal electroretinography, mfERG) preoperatively and at 1, 3, and 5 weeks after surgery. The expression of PKC alpha was examined at all three time points using immunohistochemistry, and PKC alpha mRNA levels were quantified using real-time polymerase chain reaction (PCR). Immunohistochemistry for glial fibrillary acidic protein (GFAP) and hematoxylin and eosin staining was employed to monitor the extent and dynamics of the morphological response.

Results

The full-field ERG revealed a significant increase in b-wave amplitudes derived from the isolated rod response (blue light) at all three time points after surgery (p?Conclusions Focal laser treatment in the rabbit eye induces local and wide-spread alterations in both rod- and cone-mediated retinal function in the form of supernormal b-wave amplitudes in the full-field ERG and increased latency in the mfERG. The electrophysiological abnormalities are accompanied by a progressive down-regulation of the PKC alpha isoenzyme in rod bipolar cells, reaching far beyond the treated area. PKC alpha is down-regulated directly by impaired protein synthesis, and also possibly indirectly by protein consumption related to GFAP up-regulation. The results indicate that focal laser photocoagulation interferes with PKC-alpha-mediated inhibitory regulation of inner retinal signal transmission.