Effectiveness and safety of telemedical management in uncomplicated urinary tract infections.

Uncomplicated urinary tract infections (UUTI) in women are frequent reasons for consultations in general practice. We evaluated the effectiveness and safety of telemedical management at a telemedicine centre in Switzerland. Management followed evidence-based protocols, including teleprescription of an antibiotic. Consecutive UUTI patients who had a teleconsultation including the prescription of an antibiotic were followed up three days later about symptom relief, adverse events or the need to visit a doctor. Of a total of 526 eligible women, follow-up information was available for 95%. Three days after teleconsultation, 79% of patients reported complete symptom relief, and 92% reported a reduction of UUTI symptoms. Five percent of patients reported deterioration, e.g. due to an increase of pain, flank pain or fever. Four percent reported side-effects of the prescribed antibiotics. In the three days following teleconsultation, 4% of women consulted another health-care provider without further contacting the telemedicine centre. Another 8% of patients were referred to face-to-face consultation because they developed additional symptoms or because bacterial resistance of the prescribed antibiotic was suspected. Compared to data from the literature on UUTI, evidence-based telemedical management including teleprescription of an antibiotic is as safe and effective as prescriptions initiated by a face-to-face consultation.

Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal.

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by the activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity and phospho-CREB (cyclic AMP response element protein) levels were observed in the heart. Moreover, morphine withdrawal induces Fos expression, an enhancement of NA turnover and an increase in the total TH levels. When the selective PKA inhibitor HA-1004 was infused, concomitantly with morphine pellets, it diminished the increase in NA turnover and the total TH levels observed in morphine-withdrawn rats. However, this inhibitor neither modifies the morphine withdrawal induced Fos expression nor the increase of nonphosphorylated TH levels. The present findings indicate that an up-regulated PKA-dependent transduction pathway might contribute to the activation of the cardiac catecholaminergic neurons in response to morphine withdrawal and suggest that Fos is not a target of PKA at heart levels.

Role of PKC in regulation of Fos and TH expression after naloxone induced morphine withdrawal in the heart.

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. The present study was designed to investigate the role of protein kinase C (PKC) in this process, by estimating whether pharmacological inhibition of PKC would attenuate morphine withdrawal induced Fos expression and changes in tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced on day 8 by an injection of naloxone. Morphine withdrawal induced Fos expression and increased TH levels and NA turnover in the right and left ventricle. Infusion of calphostin C, a selective PKC inhibitor, did not modify the morphine withdrawal-induced increase in NA turnover and TH levels. However, this inhibitor produced a reduction in the morphine withdrawal-induced Fos expression. The results of the present study provide new information on the mechanisms that underlie morphine withdrawal-induced up-regulation of Fos expression in the heart and suggest that TH is not a target of PKC during morphine withdrawal at heart levels.

Alterations in protein kinase A and different protein kinase C isoforms in the heart during morphine withdrawal.

The present study was designed to investigate the possible changes of protein kinase A (PKA) and different isoforms of protein kinase C (PKC): PKC alpha, PKC delta and PKC zeta after naloxone induced morphine withdrawal in the heart. Male rats were implanted with placebo (naïve) or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received saline s.c. or naloxone (5 mg/kg s.c.). The protein levels of PKA, PKC delta and PKC zeta were significantly up-regulated in the heart from morphine withdrawal rats. By contrast, morphine withdrawal induced down-regulation of PKC alpha. These results suggest that both PKA and PKC may be involved in the cardiac adaptive changes observed during morphine withdrawal.

Inhibition of protein kinase C but not protein kinase A attenuates morphine withdrawal excitation of rat hypothalamus-pituitary-adrenal axis.

Our previous studies have shown an enhanced activity of the hypothalamus-pituitary-adrenocortical axis response in rats withdrawn from morphine, which results from an increase in the hypothalamic paraventricular nucleus noradrenergic activity that is dependent on alpha-adrenoceptor activation. The first objective of this work was to examine the effect of protein kinase A (PKA) and protein kinase C (PKC) inhibitors on morphine withdrawal-induced changes in corticosterone release (an index of the hypothalamus-pituitary-adrenocortical axis activity) and in catecholaminergic turnover in the paraventricular nucleus. Plasma corticosterone levels as well as the concentration of noradrenaline, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus were determined. The second purpose of the study was to assess whether kinase inhibitors, administered continuously through s.c. osmotic minipumps, get into the brain. Chronic pretreatment for 7 days with the selective PKA inhibitor N-(2'guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004) concomitantly with morphine did not affect the increase in corticosterone release observed after naloxone-precipitated morphine withdrawal. However, pretreatment with the selective PKC inhibitor, calphostin-C significantly antagonized the corticosterone hypersecretion in morphine-withdrawn rats. Neither HA-1004 nor calphostin-C co-administered with morphine for 7 days did modify the morphine withdrawal-induced increase in noradrenaline turnover. Pretreatment with HA-1004 inhibits the increase in dopamine turnover during morphine withdrawal, whereas calphostin-C did not affect the DOPAC/dopamine ratio. Our results might indicate that expression of morphine dependence for hypothalamus-pituitary-adrenocortical axis hyperactivity involves PKC but not PKA signaling mechanisms. It is suggested that in rats PKC may be up-regulated during morphine dependence. High-performance liquid chromatography (HPLC) analysis of hypothalamic tissue from rats perfused with kinase inhibitors demonstrates that both calphostin-C and HA-1004 can cross the blood-brain barrier when administered peripherally.