Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions

Previous studies have shown the antidotal efficacy of topical iodine at 15 and 30 min post-exposure to sulfur mustard (SM). Here we demonstrate efficacy at longer intervals (20, 30, 45, and 60 min, respectively, for data) using an improved topical povidone-iodine preparation termed N66, which contains steroidal and non-steroidal anti-inflammatory agents. In the mouse, N66 reduced severity of ear edema by 43, 47, 44, and 36%; ear epidermal ulceration by 74, 58, 45, and 58%; and epidermal necrosis by 54, 34, 26, and 31% at the respective time points. A similar effect was observed with encrustation. The healing marker, grade of acanthotic area, showed dramatic increases of 39.6-, 25.3-, 20.9-, and 22-fold. Severity of the dermal parameters, acute inflammation and dermal necrosis, was reduced by 63, 34, 34, and 38% and 80, 54, 54, and 59%, respectively. In guinea pig skin, topical treatment with N66 45 min post-exposure reduced the SM-induced ulceration area by 75%. The histological parameters subepidermal microblister formation, epidermal ulceration, epidermal necrosis, and encrustation were reduced by 63, 61, 41, and 41%, respectively. The healing marker, grade of acanthotic area, was elevated by 73%. N66 induced a statistically significant reduction in two dermal markers for tissue damage: acute inflammation (33%) and dermal necrosis (48%). Reduced skin damage was also observed in areas adjacent the treated sites. The pharmacologically active components of N66 showed additive effect. These findings suggest that the povidone-iodine preparation combined with anti-inflammatory agents functions as a potent antidote against skin lesions induced by SM at relatively long intervals between exposure and treatment.Part of this work was presented at the 41st Annual Meeting of the American Society of Toxicology, Nashville, TN, March 17–21, 2002.     

Tear examinations in primary peripheral lipid keratopathy

The authors report a case of a bilateral peripheral lipid keratopathy, rising differential diagnostic points as well. After several year-long follow-up period the peripheral corneal opacity left the center unaffected. The diagnosis was confirmed by tear examinations which disclosed elevated level of fatty and phosphorous content compared to healthy control eyes.     

Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.     

Arterial splenic calcifications in children with AIDS: two case reports

Splenic calcifications in AIDS patients are usually round and result from infections with opportunistic pathogens such as Pneumocystis carinii, Mycobacterium avium-intracellulare and Cytomegalovirus. We describe here a remarkable echopattern of the spleen in two pediatric patients, resulting from linear, branching calcifications in the splenic parenchymal arteries. We believe this echopattern represents the ultrasonographic manifestation of an HIV-associated vasculopathy.     

A fully automated [35S]GTPgammaS scintillation proximity assay for the high-throughput screening of Gi-linked G protein-coupled receptors

The diversity of physiological functions mediated by the GPCR superfamily provides a rich source of molecular targets for drug discovery programs. Consequently, a variety of assays have been designed to identify lead molecules based on ligand binding or receptor function. In one of these, the binding of [(35)S]GTPgammaS, a nonhydrolyzable analogue of GTP, to receptor-activated G-protein alpha subunits represents a unique functional assay for GPCRs and is well suited for use with automated HTS. Here we compare [(35)S]GTPgammaS scintillation proximity binding assays for two different G(i)-coupled GPCRs, and describe their implementation with automated high-throughput systems.     

Acute sports-related spinal cord injury: contemporary management principles

Improvements in helmet and equipment design have led to significant decreases in overall injury incidence, but no available helmet can prevent catastrophic injury to the neck and cervical spine. The most effective strategy for preventing this type of injury appears to be careful instruction, training, and regulations designed to eliminate head-first contact. The incidence of football-related quadriplegia has decreased from a peak of 13 cases per one million players between 1976 and 1980 to 3 per million from 1991 to 1993, mostly as a result of systematic research and an organized effort to eliminate high-risk behavior. An episode of transient quadriparesis does not appear to be a risk factor for catastrophic spinal cord injury. Torg reported that 0 of 117 quadriplegics in the National Football Head and Neck Injuries Registry recalled a prior episode of transient quadriparesis, and 0 of the 45 patients originally studied in his transient quadriparesis cohort have subsequently suffered quadriplegia. The significance of developmental spinal stenosis is unclear. Plain radiographic identification of a narrow spinal canal in a player sustaining cervical cord neurapraxia warrants further evaluation by MRI to rule out functional stenosis. The presence of actual cord deformation or compression on MRI should preclude participation in high-risk contact or collision sports.     

A whole genome association study in multiple sclerosis patients from north Portugal

Genetic factors are known to influence susceptibility to multiple sclerosis (MS) but the genes involved are largely undefined. Here, we report an association study based on 200 patients and 200 controls from the Porto region in Portugal. A total of 3974 markers were successfully typed from which we have identified 46 markers showing evidence of association. When compared to a physical map three regions were found with two of these markers less than 1.5 Mb apart: chromosomes 6p21.3 (the MHC region), 6q14.1 and 7q34.     

Demonstration of increasing standard pH value of lacrimal fluid with increase of flow rate

PURPOSE: To test the hypothesis that pH value of human tears is affected by flow rate. METHODS: After stimulation with a drop of 70% alcohol into the ipsilateral nasal cavity tears from the left eyes of 30 healthy volunteers were collected with glass capillaries while flow rate of tear secretion was registered. The pCO(2), actual and standard pH were determined in the collected samples with the Astrup method: Standard pH is defined as the pH of the sample that has been equilibrated at 37 degrees C with a gas mixture having pCO(2)=40 mmHg. RESULTS: The flow rate correlated positively and significantly with both the standard pH value (r=0.503, p<0.01) and the pCO(2) (r=0.517, p<0.01) while there was no correlation between the actual pH and the flow rate. CONCLUSION: Loss of CO(2) from the sample is a cause of serious uncertainty in tear pH determination. A positive flow rate-pH relationship was found for human tears when the uncertainty was removed by determination of the standard pH.     

Molecular and epidemiological characteristics of blood-borne virus infections among recent immigrants in Spain

The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country.