Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

OBJECTIVES: A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. STUDY DESIGN: This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. METHODS: Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. RESULTS: A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. CONCLUSIONS: The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS.

Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin-coated vesicles: dependence on protein kinase A-mediated NHE3 phosphorylation.

Dopamine (DA) is a key hormone in mammalian sodium homeostasis. DA induces natriuresis via acute inhibition of the renal proximal tubule apical membrane Na(+)/H(+) exchanger NHE3. We examined the mechanism by which DA inhibits NHE3 in a renal cell line. DA acutely decreases surface NHE3 antigen in dose- and time-dependent fashion without altering total cellular NHE3. Although DA(1) receptor agonist alone decreases surface NHE3, simultaneous DA(2) agonist synergistically enhances the effect of DA(1). Decreased surface NHE3 antigen, caused by stimulation of NHE3 endocytosis, is dependent on intact functioning of the GTPase dynamin and involves increased binding of NHE3 to the adaptor protein AP2. DA-stimulated NHE3 endocytosis can be blocked by pharmacologic or genetic protein kinase A inhibition or by mutation of two protein kinase A target serines (Ser-560 and Ser-613) on NHE3. We conclude that one mechanism by which DA induces natriuresis is via protein kinase A-mediated phosphorylation of proximal tubule NHE3 leading to endocytosis of NHE3 via clathrin-coated vesicles.

Dual mechanisms of regulation of Na/H exchanger NHE-3 by parathyroid hormone in rat kidney.

Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule sodium absorption via suppression of the apical membrane Na/H exchanger (NHE-3). We examined the mechanisms by which PTH inhibits NHE-3 activity by giving an acute intravenous PTH bolus to parathyroidectomized rats. Parathyroidectomy per se increased apical membrane NHE-3 activity and antigen. Acute infusion of PTH caused a time-dependent decrease in NHE-3 activity as early as 30 min. Decrease in NHE-3 activity at 30 and 60 min was accompanied by increased NHE-3 phosphorylation. In contrast to the rapid changes in NHE-3 activity and phosphorylation, decrease in apical membrane NHE-3 antigen was not detectable until 4-12 h after the PTH bolus. The decrease in apical membrane NHE-3 occurred in the absence of changes in total renal cortical NHE-3 antigen. Pretreatment of the animals with the microtubule-disrupting agent colchicine blocked the PTH-induced decrease in apical NHE-3 antigen. We propose that PTH acutely cause a decrease in NHE-3 intrinsic transport activity possibly via a phosphorylation-dependent mechanism followed by a decrease in apical membrane NHE-3 antigen via changes in protein trafficking.

Acute inhibition of Na/H exchanger NHE-3 by cAMP. Role of protein kinase a and NHE-3 phosphoserines 552 and 605.

Regulation of the renal Na/H exchanger NHE-3 by protein kinase A (PKA) is a key intermediate step in the hormonal regulation of acid-base and salt balance. We studied the role of NHE-3 phosphorylation in this process in NHE-deficient AP-1 cells transfected with NHE-3 and in OKP cells expressing native NHE-3. A dominant-negative PKA-regulatory subunit completely abolished the effect of cAMP on NHE-3 activity demonstrating a role of PKA in the functional regulation of NHE-3 by cAMP. NHE-3 isolated from cAMP-treated cells showed lower phosphorylation by purified PKA in vitro suggesting that NHE-3 is a PKA substrate in vivo. Although changes in NHE-3 whole protein phosphorylation is difficult to detect in response to cAMP addition, the tryptic phosphopeptide map of in vivo phosphorylated NHE-3 showed a complex pattern of constitutive and cAMP-induced phosphopeptides. To test the causal relationship between phosphorylation and activity, we mutated eight serines in the cytoplasmic domain to glycine or alanine. Single or multiple mutants harboring S552A or S605G showed no PKA activation or reduced regulation by PKA activation. Ser-552 and Ser-605 were phosphorylated in vivo. However, multiple mutations of serines other than Ser-552 or Ser-605 also reduced the functional PKA regulation. We conclude that regulation of NHE-3 by PKA in vivo involves complex mechanisms, which include phosphorylation of Ser-552 and Ser-605.

Behavioral effects of methyl parathion and toxaphene exposure in rats.

The behavior of rats exposed peri- and postnatally to methyl parathion (MP) and toxaphene (T) was examined with a variety of maturational and learning tests. Females received daily oral doses of 1.0 mg/kg MP or 1.0 mg/kg MP + 2.0 mg/kg T between Days 7-15 of pregnancy. With T alone, rats of the postnatal group were dosed daily with 6 mg/kg for 21 days, while in the perinatal study females received 6 mg/kg daily from Day 7 of pregnancy until parturition. Rat pups exposed to sublethal doses of MP and T in combination or alone demonstrated few significant changes in learning ability as measured by a simple two-choice maze, motor skills, or behavior.

Bioelectrical activity of isolated ventral nerve cords of the cockroach, Periplaneta americana L., treated with toxaphene.

Effects of toxaphene were studied with the ventral nerve cord (VNC) of the cockroach, Periplaneta americana (L). Intense forms of activity were observed in isolated nerve preparations treated with toxaphene. Latent periods between introduction of toxaphene and onset of intense activity decreased as the concentrations were increased.

Ion movements in the nervous system of the American cockroach, Periplaneta americana (L.), influenced by toxaphene.

The effect of toxaphene upon ion fluxes of the central nervous system (CNS) of the cockroach, Periplaneta americana (L.), was studied in vitro. The CNS, divided into three sections (brain, thoracic, and abdominal), was exposed to 10(-5) M toxaphene in saline containing 24Na+, 42K+, 36CL-, or 45Ca++. Uptake and efflux of these ion were evaluated. Toxaphene was responsible for significant increases in the internal levels of 42K+ and 45Ca++, but had little effect upon 24Na+ or 36Cl- movements. The resulting concentration changes of the ions may be involved in the neural activity observed with toxaphene poisoning. Of the three CNS sections, significant changes were more numerous and occurred earlier in abdominal sections.

Uptake of 36Cl-toxaphene in mosquito fish, Gambusia affinis.

The toxicity syndrome of toxaphene to G. affinis was divided into 5 stages, and the residue level at each stage was determined. By the time fish were exhibiting the first toxicity response (stage 2), 90.3% of the mean fatal residue level had been sorbed. Regression analysis indicated that sorption of toxaphene is a linear function with respect to time. Excretion was not observed following an 8 hour exposure to 2ppm toxaphene. Metabolic alteration of toxaphene during the experiments appeared to be minimal. Differences in individual mortality appeared to be due to differences in uptake rather than differences in ability to tolerate particular body loads of toxaphene.