Psychological Trauma and LGBT Caregivers: A Conceptual Framework to Guide Practice.

LGBT adults face unique risk factors such as social isolation, discrimination, and victimization, and occasionally th ey engage in detrimental behaviors like high alcohol and drug use and risky sexual activity that negatively impacts psychological/physical health. These risks can affect their overall health and stress the relationship with an older caregiver/recipient-partner following exposure to acute medical event. The experience of an acute medical event among a LGBT caregiving partner can result in psychological trauma. In this article the authors present a conceptual framework involving stress process theory, life course theory, and family systems perspective to understand the effect of stressors on LGBT caregiving partners. Implications for social work practice include assessing, coordinating care, counseling and negotiating services at micro level, engaging family-centered approaches to support positive transition to caregiving role at mezzo level, and advocating for policy and cultural shifts to supports and diminish stigma of this group.

Caregivers of veterans with "invisible" injuries: what we know and implications for social work practice.

Today, as a result of the longest volunteer-fought conflict in U.S. history, there are many wounded coming home not only with posttraumatic stress disorder (PTSD), but also with traumatic brain injury (TBI), which together have been called the "signature" or "invisible" injuries of the Iraq and Afghanistan wars. Caregivers are an important part of their recovery, yet little is known about them, as previous research on caregivers mostly focused on geriatric populations. According to one estimate 275,000 to 1 million people are currently caring or have cared for loved ones who have returned from Iraq and Afghanistan. These caregivers are unique in that they are younger, some with children, and they are caring for a unique under-studied population for longer periods of time. This article summarizes literature on caregivers of veterans who suffer from PTSD, TBI, or both; provides a theoretical framework; and discusses implications for social workers in assisting caregivers and their families.

Lyme borreliosis--waiting for Lyme carditis? A long-term prospective study.

A long-term prospective study of patients with confirmed non-cardiac form of Lyme disease (n=221) over a mean follow-up period of 40.6 months is reported. The study revealed no case of Borrelia-related cardiac involvement developed after several years in patients who had received antibiotic therapy in the early period. Therefore, these patients do not need follow-up by a cardiologist.

[Cardiac abnormalities of lyme borreliosis]. / Postizení srdce v prubehu lymeské borreliózy.

The article summarizes basic characteristics of Lyme borreliosis, its incidence, epidemiology, pathogenesis and clinical image. Particular attention is given to the review of papers aimed at the cardiac abnormalities--the Lyme carditis. Though they are not very frequent, due to the variability of their clinical course and due to various forms, which are difficult to diagnose, they can represent a specific problem. Major part of the article is given to the authors' own experience with the dilated cardiomyopathy of the Borrelia origin and namely to the perspective study of the patients after the skin form of the disease erythema migrans, who were treated "lege artis" in the early phase of the disease with antibiotics. Authors were interested how many of those patients would develop later the cardiac abnormalities.

[Prevalence of antiborrelia antibodies in two populations: various interpretations of the same data]. / Prevalence antiborreliových protilátek u dvou populací: ruzná interpretace stejných dat.

OBJECTIVE: The objective of the work was to test whether differently formulated hypotheses, when using correct statistical methods, and the same data lead to the same results. The work pertains to the interpretation of the prevalence of antiborrelia antibody levels in more or less high risk populations. GROUP: A group of 200 blood donors from Prague (100 men, mean age 33.5 years and 100 women mean age 24.4 years) and 71 subjects with a higher risk of contact with ticks infected with Borrelia burgdorferi--forestry workers from the Sumava mountains (39 men, mean age 40.6 years and 32 women, mean age 44.5 years). METHOD: In all participants antiborrelia antibodies class IgM and IgG were assessed and using the Western blot method the presence of specific antigens was examined. The blood samples of all probands were analyzed in the national reference laboratory for Lyme borreliosis CEM in the National Institute of Public Health in Prague. To test the hypothesis on the difference of groups as regards the frequency of positive antibody levels the chi square test was used. For testing the hypothesis on the difference of the groups as regards antibodies irrespective of normal laboratory values the non-parametric method--the Mann-Whitney test was used. RESULTS: The group of Prague blood donors and forestry workers from the Sumava mountains do not differ as to the individual frequency of positive antibody values assessed by the ELISA method in class IgM and IgG but they differ in class IgM assessed by the Western blot method. Both groups differ moreover markedly in the general distribution of antibodies unrelated to normal laboratory values assessed by the ELISA method in class IgM, in class IgG the distribution does not differ. CONCLUSION: We provided evidence that when using a different formulation of the hypothesis while using correct statistical methods identical data can be differently interpreted. Thus in the interpretation of the prevalence of antiborrelia antibody levels in healthy populations with a different risk--even if the two groups do not differs as to the frequency of positive findings, there is a significant statistical difference in their distribution.

Borrelia infection as a cause of carditis (a long-term study).

BACKGROUND: Although the frequency of Lyme carditis is not high, it is one of the most challenging conditions in terms of diagnosis. No long-term studies that would help expand our body of knowledge concerning the circumstances of its development and the natural course of this form of Lyme borreliosis (LB), the most widespread anthropozoonosis in Central Europe, have been reported to date. AIM: The authors sought to describe and assess the consequences of a less common form of Lyme carditis (LC). An assessment of the following aspects was made: a) the forms, natural history and sequelae of the less common clinical appearances of LC, b) the role of antibiotic therapy with reference to the late manifestations of LB. METHODS: Three patients were selected from a group of 60 consecutive patients with demonstrated LC during a follow-up period from 1987 to 2000. Patient no. 1 was being followed for myocarditis with frequent ventricular extrasystoles, patient no. 2 for pericarditis, and patient no. 3 for dilated cardiomyopathy as a late manifestation of LB. In addition to routine examination at entry, the patients were subjected to a standard 12-lead ECG, continuous 24-hour Holter ECG monitoring, exercise testing (bicycle ergometry), investigations of antibodies using ELISA and Western blot, investigation of thyroid (T3, T4, TSH tests) and mineral levels. RESULTS: The study showed no significant correlation between the clinical course and levels of specific antibodies. It confirmed the concept that inadequate or no therapy with antibiotics in the initial stage of the disease has a significant effect on the development of late sequelae. CONCLUSION: Based on the long-term treatment of three patients with less common, yet clinically urgent findings, the authors conclude that even a relatively serious clinical course is associated with no major limitations for affected individuals after an interval of several years.

[Informational value of the prevalence of antiborrelia antibodies in a healthy and at risk population]. / Výpovední hodnota prevalence antiboreliových protilátek u zdravé a rizikové populace.

The authors tried to confirm data on the prevalence of antiborrelia antibodies class IgM and IgG in the local healthy population (200 blood donors) and in subjects with an increased risk of infection (forestry labourers, forestry workers and huntsmen). All blood samples were analyzed in the National Reference Laboratory for Lyme borreliosis CEM (LB) in the National Institute of Public Health in Prague by the ELISA NRLB KC 90 method and in case of a positive result they were confirmed by the Western blot Lyme method. All patients completed a special questionnaire used as a standard procedure in the consultation centre for LB. In the group of blood donors 100 men were examined, mean age 33.5 years and 100 women, mean age 24.4 years. In 26 positive antibodies against Borrelia burgdorferi (Bb) were confirmed, but on invitation to medical examination only 22 attended, 11 men and 11 women (10.1%). Examination of antiborrelia antibodies by the ELISA method proved positivity of class IgM 7 times and of class IgG 9 times. By the Western blot method (WB) class IgG was confirmed three times. In the risk group 39 men were examined, mean age 40.6 years and 32 women. In 12 of them (17.9%) positivity of antiborrelia antibodies against Borrelia burgdorferi (Bb) was proved by the ELISA method as well as the WB method. If the percentage confidence interval of the control group is taken as a basis for comparison, then the value of the risk group is within this interval at a significance value of alpha = 0.01. In the conclusion the authors discuss the problem of interpretation of positive serological results and the pitfalls of their evaluation not only from the aspect of validity of laboratory findings, due to the absence of standardization of methods, but also with regards to obscure aspects of the persistence of IgM antibodies after years of lege artis antibiotic treatment.

Glucocorticoid metabolism in proximal tubules modulates angiotensin II-induced electrolyte transport.

The hormonal interactions that regulate electrolyte transport in the proximal tubule are complex and incompletely understood. Since endogenous glucocorticoids and angiotensin II each can affect electrolyte transport in this renal segment, we hypothesized that local metabolism of glucocorticoids by the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) might alter the response to angiotensin II. Studies were conducted in cultured origin defective SV-40 transformed immortalized renal proximal tubule cells (IRPTC) derived from weanling Wistar rat kidney. The 11beta-HSD contained in these cells uses NADP+, has an apparent Km for corticosterone of 1.6 microM, but functions only as a dehydrogenase (corticosterone --> 11-dehydro-corticosterone). When mounted in modified Ussing chambers, IRPTC generate a transmembrane current, and angiotensin II (10 pM to 10 microM) increases this sodium-dependent current. Cells incubated with corticosterone (100 nM) and the 11beta-HSD inhibitor carbenoxolone (CBX) (1 microM) for 24 hr and then acutely stimulated with angiotensin (10 nM) show a greater rise in current than do cells exposed to corticosterone alone and stimulated with angiotensin (corticosterone + CBX: 64.2% +/- 20.5% vs. corticosterone: 18.8% +/- 5.9%; P < 0.02 at 180 min)[mean +/- SE percentage above baseline, n = 8/group]. Cells exposed to corticosterone (100 nM) or CBX (1 microM) alone for 24 hr and then stimulated with angiotensin II (10 nM) had responses similar to controls. Thus glucocorticoids can enhance angiotensin II-induced electrolyte transport in proximal tubule epithelial cells when local 11beta-HSD is inhibited.

Glucocorticoids inhibit the expression of calcium-dependent potassium channels in vascular smooth muscle.

Increased calcium-activated potassium channel (KCa) activity in vascular smooth muscle (VSM) cells leads to a relaxation response counteracting the effects of high blood pressure. Since chronic exposure to glucocorticoids (GC) can be associated with an increase in blood pressure, we reasoned that GCs might modify the expression of KCa channels resulting in a net rise in vascular tone. To test this hypothesis, primary cultures of rat VSM cells were exposed to (a) RU 28362 (a pure glucocorticoid receptor agonist), 1 microM; (b) corticosterone 10 nM + carbenoxolone (an inhibitor of bidirectional VSM 11beta-OH steroid dehydrogenase), 1 microM; (c) 11-dehydrocorticosterone (a biologically inactive metabolite), 10 nM + carbenoxolone; (d) carbenoxolone alone; or (e) aldosterone 10 nM for periods of up to 72 h. Proteins were then extracted and Western blots prepared. Gels were probed with a rabbit-derived polyclonal antibody directed against KCa channel protein. The experimental procedure was repeated on separate sets of VSM cells to ensure reproducibility. Expression of KCa channel protein was diminished in VSM cells incubated with corticosterone + carbenoxolone and with RU 28362 after 24 h and remained low at 72 h. Expression of KCa protein in cells exposed to 11-dehydrocorticosterone + carbenoxolone, carbenoxolone alone, and aldosterone was either similar to controls or mildly increased over the 72 h. These data are consistent with the hypothesis that GCs diminish the expression of KCa protein. Diminished KCa expression could contribute to the observed increase in vascular tone following chronic GC exposure.

Effect of serum on vascular smooth muscle function.

Serum contains many biologically active factors influencing cell growth and is commonly used as a culture medium supplement. It has not generally been appreciated that serum can affect vascular tone. We have observed that the contractile response of aortic rings previously exposed to 10% fetal bovine serum (FBS) for 24 hours and then stimulated with phenylephrine (0.01-1microM) or angiotensin II (1microM) is significantly diminished compared to 1) rings incubated in FBS for only 6 hours, 2) aortic rings previously incubated in 1% FBS or 3) aortic rings incubated in 10% bovine serum albumin for 24 hours. A similar attenuated response was also seen when the vascular aortic rings were incubated in heat inactivated adult bovine serum. To test whether prostaglandins might be induced by factors contained in serum and account for the diminished stimulated contractile response, rings were incubated for 24 hours in media containing 10% FBS with either indomethacin 10microM, corticosterone 100nM or 11-dehydrocorticosterone 100nM. These agents are known to affect prostaglandin synthesis. Contractile responses were then measured accordingly. In each series, the previously attenuated contractile response to phenylephrine and to angiotensin II was fully restored with prostaglandin synthesis inhibition. Thus, factors contained in serum are capable of blunting the stimulated contractile response of rat aortic vessels. These serum factors appear to act by inducing prostaglandin synthesis in vascular tissue.

Localization of 2 11beta-OH steroid dehydrogenase isoforms in aortic endothelial cells.

11Beta-hydroxysteroid dehydrogenase (11beta-HSD) is expressed in vascular smooth muscle cells (VSMC) but has not been reported to be present in vascular endothelial cells. This enzyme assists in regulating the cellular concentration of active endogenous glucocorticoids (GCs). We have observed that endothelium intact rat aortic rings express message for both Type 1 and Type 2 11beta-HSD whereas primary cultures of VSMC express only mRNA for the Type I isoform. Since GCs diminish prostacyclin synthesis in endothelial cells, we hypothesized that 11beta-HSD is present in vascular endothelial cells. In primary cultures of rat aortic endothelial (RAE) cells, mRNA from both isoforms of 11beta-HSD could be detected by RT-PCR with higher levels of the Type 1 isoform. The oxo-reductase reaction "activating" 11-dehydro metabolites back to the parent steroid is the preferred enzyme direction (12:1 after a 120 minutes steroid incubation) in intact RAE cells. When RAE cells are grown in the presence of antisense oligonucleotides specific for Type 1 11beta-HSD, oxo-reductase activity is decreased by approximately 50% but the dehydrogenase reaction, which inactivates endogenous GCs and is characteristic of the Type 2 isoform, is unaffected. Thus endothelial cells appear to express both isoforms of 11beta-HSD; the Type 1 isoform dominates functioning in the oxo-reductase mode. Inhibition of the oxo-reductase reaction may lower the local concentrations of GC and indirectly allow for increased production of prostacyclin in endothelial cells.

11BetaOH-progesterone affects vascular glucocorticoid metabolism and contractile response.

Vascular smooth muscle (VSM) contains a bidirectional isoform of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), the enzyme that can metabolize endogenous glucocorticoids to their respective 11-dehydro derivatives. 11BetaOH-progesterone (11betaOH-P), a compound that can be produced in vivo, is as potent or more potent than licorice derivatives in inhibiting renal and hepatic 11beta-HSD. When studied in homogenates prepared from primary cultures of rat VSM, 11betaOH-P and its derivative, 11-keto-progesterone (11-keto-P), proved to be potent, directionally specific inhibitors of vascular 11beta-HSD. 11BetaOH-P selectively inhibited the forward dehydrogenase reaction (corticosterone-->11-dehydrocorticosterone), whereas 11-keto-P selectively blocked the reverse oxidoreductase reaction. To test the physiological effects, vascular rings were prepared from rat aorta. Rings were incubated in culture media containing either a submaximal concentration of corticosterone (10 nmol/L), 11-dehydrocorticosterone (100 nmol/L), 11betaOH-P (1 micromol/L), 11-keto-P (1 micromol/L), or a combination of glucocorticoid and inhibitor for 24 hours. After the 24-hour incubation, rings were briefly stimulated sequentially with phenylephrine (10 nmol/L to 1 micromol/L) and angiotensin II (1 micromol/L). The immediate contractile response in rings incubated with both corticosterone and 11betaOH-P was greater than in rings previously incubated with either the corticosterone or 11betaOH-P alone (eg, response to 100 nmol/L phenylephrine in milligrams of force, mean+/-SE: corticosterone, 728+/-56, n=9; 11betaOH-P, 325+/-105, n=4; both, 1132+/-122, n=8; corticosterone versus both, P<.01). In contrast, the immediate contractile responses to phenylephrine and to angiotensin II were attenuated in rings exposed previously to both 11-dehydrocorticosterone and 11-keto-P. Thus, 11betaOH-P and 11-keto-P (and possibly structurally similar compounds) alter the vascular effects of glucocorticoids and may play a role in glucocorticoid-induced hypertension.

Influence of dietary sodium on the renal isoforms of 11 beta-hydroxysteroid dehydrogenase.

Endogenous glucocorticoids are converted to their biologically inert 11-dehydroderivatives by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). The low-K(m), NAD(+)-dependent renal isoform (Type 2) identified in the distal nephron protects mineralocorticoid receptors from activation by endogenous glucocorticoids. The function of high-K(m), NADP(+)-dependent renal isoform (Type 1) is less well understood. Since glucocorticoids may modulate sodium transport in renal proximal tubules (PT), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na(+)-11 beta-HSD activity was assessed in homogenates of canine PT by the conversion of cortisol to cortisone in the presence of NADP+ 200 microM. A high-Na+ diet for 4 days increased the Vmax 4-fold, with no change in the Type 1 K(m) (40 mEq/day Na+ diet: K(m) 0.959 microM, Vmax 3.40 pmoles/min/mg protein versus 150 mEq/day Na+ diet: K(m) 0.962 microM, Vmax 14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+ diet produced no detectable change in the Type 2 isoform enzyme kinetics and mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11 beta-HSD can be regulated by dietary Na+ independent of changes in the renal Type 2 isoform.

Effects of licorice derivatives on vascular smooth muscle function.

Vascular smooth muscle contains a bidirectional form of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) which can inactivate (dehydrogenase) endogenous circulating glucocorticoids (GCs) or activate (oxo-reductase) 11-dehydro-metabolites by their conversion back to the parent steroid. Enzyme direction in vascular smooth muscle (VSM) has potential physiological consequences since GCs may enhance the response to known vasoconstrictors. We determined that carbenoxolone is a competitive inhibitor of 11beta-HSD contained in VSM cells with a lower Ki for forward dehydrogenase reaction (0.02 microM) compared to the oxo-reductase reaction (0.41 microM). To test whether changes in enzyme directional activity can affect the contractile response, aortae from adrenally intact Sprague Dawley rats were removed and sectioned into 2.5 mm rings. Rings were incubated with corticosterone 10 nM plus carbenoxolone (CBX) 10 microM (a concentration well above the Ki for both the dehydrogenase and oxo-reductase reaction) for 24 hrs. These rings showed an enhanced dose dependent contractile response to phenylephrine (PE) 0.01 microM(-1) microM and to angiotensin II 1 microM compared to rings incubated with corticosterone alone, CBX alone, or controls: [e.g. response to PE 1 microM in mg of contractile force, mean +/- SE: corticosterone plus CBX 1495 +/- 162 (n=10) vs corticosterone 1039 +/- 64 (n=9), p<0.05]. Aortic rings preincubated with 11-dehydrocorticosterone 10(-7)M and CBX 10 microM displayed a decreased contractile response compared to 11-dehydrocorticosterone alone. Thus in situ glucocorticoid metabolism is important in mediating the constrictor responses of vascular tissue.

Glucocorticoid metabolism in the newborn rat heart.

A relative cardiac hypertrophy has been observed in newborns chronically treated with dexamethasone. To test the hypothesis--that dexamethasone might alter steroid metabolism within the heart--rat pups were injected with vehicle, corticosterone (dosages 20 or 200 micrograms/pup/injection, or 1 mg/pup/injection) or dexamethasone (5 micrograms/pup/injection) on Day 2-6 and sacrificed on Day 7-8. Injections with dexamethasone in this dosage have induced the cardiac changes in this rat model. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) activity was assessed in hearts from these adrenally intact rat pups by incubating tissues with 3H-corticosterone 10(-8) M for 60 min. On Day 7-8, controls transformed 10.3% +/- 1.1% (mean +/- SE) of the corticosterone (Compound B) to 11-dehydrocorticosterone (Compound A) generating 1.25 +/- 0.35 x 10(-12) moles A/mg protein (n = 8). Tissues from pups pretreated with corticosterone at all three dosages were not different from controls in percent metabolized and moles A/mg generated. In contrast, hearts from dexamethasone treated pups transformed only 4.5% +/- 1.0% of the corticosterone to A generating 3.19 +/- 0.05 x 10(-13) moles A/mg protein (n = 10) (P < 0.05 versus control in moles/mg protein metabolized). Cultured cardiomyocytes exposed to dexamethasone for 4 days in vitro also decreased their expression of 11 beta-OHSD mRNA. Readily metabolized endogenous glucocorticoids produced little or no effect on developing heart muscle while treatment with dexamethasone, a potent synthetic glucocorticoid, induced relative cardiac hypertrophy and downregulated 11 beta-OHSD mRNA expression and enzyme activity.

Bidirectional activity of 11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle cells.

Endogenous glucocorticoids (GC) can be metabolized through the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD); in the rat, corticosterone (B) is converted to its inactive metabolite 11-dehydrocorticosterone (A). Since increased tissue concentrations of GCs may affect blood pressure by potentiating the vasoactive effects of alpha-adrenergic agonists and possibly other pressors, we studied the metabolism of corticosterone in freshly dissected aortae and cultured vascular smooth muscle cells (VSMC). Incubations were generally conducted for 60 min with 10(-8) M steroid; steroids were isolated and identified by HPLC. In aortic minces stripped of endothelium, the oxo-reductase reaction of A back to B was nearly 4 times greater than the dehydrogenase reaction of B to A (2.8 +/- 0.5 x 10(-11) versus 7.3 +/- 1.0 x 10(-12) mol/mg protein). This pattern was also seen in cultured VSMC during growth and quiescent states (growth A to B 3.2 +/- 0.4 x 10(-12) versus B to A 9.7 +/- 0.9 x 10(-13) mol/mg protein; quiescent A to B 8.8 +/- 0.1 x 10(-12) versus B to A 1.2 +/- 0.2 x 10(-12) mol/mg protein). Enzyme activity in either direction was less during growth, correlating with a decrease in mRNA for 11 beta-OHSD. In cell homogenates containing 200 microM NADP(H), the enzyme functioned equally in either direction at pH 7.4 with an apparent Km for corticosterone of approximately 2 x 10(-7) M. Carbenoxolone, an inhibitor of 11 beta-OHSD, suppressed the dehydrogenase reaction to a greater degree than the reverse oxo-reductase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)