Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.

The King Baboon spider, , is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from , but the molecular basis by which the venom induces pain is unknown.

Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi.

Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi.

The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity.

Voltage-gated sodium (Na) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal Na channels inhibiting peak current of hNa1.

Pharmacological characterisation of the highly Na1.7 selective spider venom peptide Pn3a.

Human genetic studies have implicated the voltage-gated sodium channel Na1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits Na1.

Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain.

Loss-of-function mutations of Na(V)1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of Na(V)1.7 a promising therapeutic strategy for the treatment of pain.

Characterisation of Na(v) types endogenously expressed in human SH-SY5Y neuroblastoma cells.

The human neuroblastoma cell line SH-SY5Y is a potentially useful model for the identification and characterisation of Na(v) modulators, but little is known about the pharmacology of their endogenously expressed Na(v)s. The aim of this study was to determine the expression of endogenous Na(v) α and β subunits in SH-SY5Y cells using PCR and immunohistochemical approaches, and pharmacologically characterise the Na(v) isoforms endogenously expressed in this cell line using electrophysiological and fluorescence approaches. SH-SY5Y human neuroblastoma cells were found to endogenously express several Na(v) isoforms including Na(v)1.

Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida.

Cancer cell toxicity-guided fractionation of extracts of the Papua New Guinea marine cyanobacteria Lyngbya majuscula and Lyngbya sordida led to the isolation of apratoxin D (1). Compound 1 contains the same macrocycle as apratoxins A and C but possesses the novel 3,7-dihydroxy-2,5,8,10,10-pentamethylundecanoic acid as the polyketide moiety. The planar structures and stereostructures of compound 1 were determined by extensive 1D and 2D NMR and MS data analyses and by comparison with the spectroscopic data of apratoxins A and C.

HIV testing among Haitian women: lessons in the recognition of risk.

Haitian women in Miami, Florida, responded to recruitment for testing of HIV antibody serostatus in ways that demonstrated the value of ethnographic methods for studying reactions to this kind of test, especially pre- and posttest counseling sessions. A total of 155 women between 14 and 61 years old, recruited in Miami in 1992 and 1993, participated. Response to testing identified three primary obstacles to the women's understanding of content presented in pre- and posttest counseling sessions: (1) their confusion about the meaning of positive versus negative, (2) the investigators' difficulty in communicating the concept of antibody, and (3) vagueness of the concept of window period between exposure and presentation of antibody.

Sex, drugs, and the spread of HIV/AIDS in Belle Glade, Florida.

Belle Glade, Florida, an agricultural community in the heart of the state's vegetable and sugar cane production areas, has the highest cumulative per capita incidence of AIDS in the United States. A risk reduction intervention program was introduced to lessen unsafe AIDS-related behaviors and to generate data on the epidemiology of HIV infection. Initial attention focused on individuals who were believed to be at the core of the transmission pattern, injection drug users and their sexual partners.

Predictors of Haitian-American infant development at twelve months.

Perinatal and early childhood influences on the development of 66 Haitian-American children were examined as part of an ongoing home visiting program. Although all participants were impoverished, approximately two-thirds lived in an urban setting with some access to social and health services, while one-third lived in a rural farmworkers' community where housing and services were sharply substandard. Measures used to examine the development of infants in these 2 settings included birthweight, household crowding, parental contributions to the child-rearing environment (the HOME), and developmental progress at 12 months on the Bayley Scales of Infant Development.

Intestinal protozoa in homosexual men of the San Francisco Bay area: prevalence and correlates of infection.

To compare the prevalence of intestinal parasitic infection in male homosexuals selected from other sources with the levels previously reported from clinic-derived populations, various homosexual groups of the San Francisco Bay Area were checked by means of stool examination and questionnaires for prevalence of intestinal parasites and for related sexual behavioral patterns during a 3-year period. The prevalence of Entamoeba histolytica (28.6%) was similar to that reported in other studies, whereas that of Giardia lamblia was lower.

Thyroid supplements: effect on bone mass.

Thyrotoxicosis and thyroid replacement therapy can cause osteopenia. The relative effects of such therapy and of aging, body size, menopausal status and smoking on bone mass were compared by measuring the combined cortical thickness (CCT) of the second metacarpal bone in 151 women taking thyroid hormone. Age was the single factor strongly related to CCT, with the mean CCT decreasing by 0.

Risk of vascular disease in women. Smoking, oral contraceptives, noncontraceptive estrogens, and other factors.

We investigated the relation in women of various factors to risk of myocardial infarction, subarachnoid hemorrhage, other strokes, and venous thromboembolism. Smoking significantly increased risk of all four diseases, whereas oral contraceptive use was associated with an increase only in risk of subarachnoid hemorrhage and venous thromboembolism. Use of noncontraceptive estrogens was not associated with increased risk of any of these diseases.

Oral contraceptives, smoking, and other factors in relation to risk of venous thromboembolic disease.

Analysis of data from the Walnut Creek Contraceptive Drug Study showed a significant increase in risk of venous thromboembolic disease in the absence of surgery, trauma, malignancy, pregnancy, and the puerperium for women with a previous history of thromboembolism, hypertension, diabetes, varicose veins, gallbladder disease, and cigarette smoking. Education, marital status, parity, use of noncontraceptive estrogens, and obesity were not associated with an increase in risk of the disease. When only cases of the disease in the absence of all known predisposing causes (idiopathic cases) were analyzed, both oral contraceptive use and smoking remained as independent risk factors; there was no evidence of a positive interaction between them.

Use of oral contraceptives, cigarette smoking, and risk of subarachnoid haemorrhage.

In a large cohort of women, the risk of subarachnoid haemorrhage was significantly associated both with cigarette smoking and with use of oral contraceptives (O.C.S.

Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins.

To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.

Concentrations of serum protein fractions in white women: effects of age, weight, smoking, tonsillectomy, and other factors;

We measured the concentrations of protein in electrophoretic fractions (albumin and alpha1-, alpha2-, beta, and gamma-globulins) of serum from 9547 white women to determine their relations to age, weight, smoking and other factors. Albumin concentration decreases with age, beta globulin concentration increases. Increasing weight is associated with a decrease in albumin, but with increases in all the globulins.

Serum protein fractions. Effects of oral contraceptives and pregnancy.

As a part of a longitudinal study to determine the side effects of oral contraceptive drugs (OCs), protein electrophoresis studies were carried out on sera obtained from 4057 current users of OCs, 9774 nonusers, and 624 women in the first trimester of pregnancy. Albumin and gamma globulin levels were lower in OC users than in nonusers; alpha-1, alpha-2, and beta fractions were higher. A similar effect was observed during the first trimester of pregnancy.

Rheumatoid factor (antigammaglobulin) in women: effects of oral contraceptives use of its prevalence.

A total of 14,856 women, including 921 pregnant subjects, were tested for rheumatoid factor; 4,562 were using oral contraceptives at the time of testing. The prevalence of rheumatoid factor increased directly with age. The age-adjusted prevalence of rheumatoid factor was lower in oral contraceptive users than in nonusers but this difference was not statistically significant.

Placental ratio in white and black women: relation to smoking and anemia.

In a study of 7,000 pregnancies it was found that, particularly in black women, hemoglobin levels were lower in smokers than in nonsmokers. This is the reverse of previously reported findings in nonpregnant persons. At delivery, the mean ratio of placental weight to birth weight (placental ratio) was higher in the infants of smokers than of nonsmokers.

Prevalence of concurrent diabetes mellitus and idiopathic facial paralysis (Bell's palsy).

Diabetes mellitus was present in 11.4 per cent of 684 patients with Bell's palsy, in 28.4 per cent of the sixty-seven with recurrent or bilateral palsy, and in 16.