Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Platelet adhesion and aggregation on polyethylene: effect of exhaustive exercise.

The aim of the present study was to evaluate the effect of an exhaustive exercise on platelet adhesion and aggregation on polyethylene (PE) in relation to changes in plasma cortisol concentration in order to ascertain the effect of physical stress response in the blood-contacting properties of polymeric materials. Twelve healthy sedentary subjects, six males and six females, were studied. Each subject performed an exercise test on a bicycle ergometer at intensity corresponding to 70% VO2 max until exhaustion. One month after the exercise session, each subject participated in a control rest session. In both sessions, blood samples were drawn every 5 min for cortisol, lactate, hemoglobin, and hematocrit determinations and every 15 min for evaluation of platelet adhesion and aggregation. Individual comparisons between the rest and exercise cortisol patterns identified three categories of cortisol responders to exercise: positive responders (C +, showing higher concentrations during exercise than during rest), negative responders (C -, showing lower concentrations during exercise than during rest), and nonresponders (NR, showing similar concentrations during exercise and rest). The results revealed that C + had lower platelet adhesion and aggregation scores during exercise than during rest; moreover C - had higher scores than C + and NR during exercise. The results obtained demonstrated no effects of sex or exercise on either cortisol plasma levels or platelet adhesion and aggregation on PE surface. With regard to cardiovascular risk, the results suggest that exercise favorably affects platelet functions when mechanisms of metabolic adaptation to prolonged muscular work, expressed by a cortisol increase, are activated during exercise.

The behavioral and neuronal effects induced by repetitive nociceptive stimulation are affected by gonadal hormones in male rats.

The role of gonadal hormones in inducing long-term modifications in response to transient nociceptive stimuli was investigated in adult male rats. Three weeks after gonadectomy or sham surgery, animals were randomly divided into groups to be exposed to sham (only a prick in the dorsal hind paw) or formalin treatment (50 microl, 5% s.c. in the dorsal hind paw) once a week for the following 3 weeks. In gonadectomized animals the formalin-induced responses (licking, flexing and jerking of the injected paw) did not differ from those of intact animals after the first formalin injection. However, their levels were higher after the second or third injections. Indeed, in intact animals the formalin-induced responses progressively decreased, being significantly lower after the third injection than after the first; in gonadectomized animals, the formalin-induced responses did not change with repetition of the formalin treatment. In intact rats, c-Fos expression in the paraventricular nucleus of the thalamus and arcuate nucleus of the hypothalamus remained at control levels or decreased in animals injected two or three times with formalin; in gonadectomized rats, c-Fos expression increased with repetition of the noxious stimulation, reaching the highest levels in animals injected three times with formalin. These results show that male gonadal hormones have an inhibitory, adaptive effect on the behavioral and neuronal responses to repeated nociceptive stimulation.

Effects of the essential oil from citrus lemon in male and female rats exposed to a persistent painful stimulation.

The ability of olfaction to modulate behavior in mammalian species has repeatedly been demonstrated. Here we tested the properties of the volatile components of lemon essential oil. Male and female rats were allowed to inhale the aroma while experiencing a persistent nociceptive input (50 microl formalin, 5%); in the same animals the c-Fos immunohistochemistry was used to test the degree of neuronal activation of areas belonging to the limbic system. In formalin-treated animals, lemon essential oil decreased licking the injected paw, in both sexes; flinching and flexing were decreased in males and increased in females in the interphase (5-20 min) of the formalin test. Essential oil increased the c-Fos expression in the arcuate n. of the hypothalamus. Essential oil and formalin increased c-Fos in the paraventricular n. of the hypothalamus and in the dentate gyrus of the hippocampus. In the paraventricular n. of the thalamus formalin induced higher c-Fos than control in both sexes; when formalin treatment was carried out in presence of essential oil, c-Fos further increased in males, but remained at control levels in females. The present results clearly indicate the ability of lemon essential oil to modulate the behavioral and neuronal responses related to nociception and pain.

Exposure to the estrogenic pollutant bisphenol A affects pain behavior induced by subcutaneous formalin injection in male and female rats.

We investigated the effects of perinatally administered bisphenol A (BPA), an environmental contaminant with estrogenic activity, on formalin-induced nociceptive responses. Male and female offspring of mother rats treated with BPA or oil were cross-fostered after birth to obtain three homogeneous groups: BPA-prenatal, receiving BPA via the placenta; BPA-postnatal, receiving BPA through suckling; OIL, control, from mothers receiving only peanut oil (vehicle). All groups underwent a pain test with s.c. formalin injection (50 microl, 10%) or were sham injected (pricking with a syringe needle) in the dorsal hind paw. They were immediately placed in an open field apparatus where pain responses (licking, flexing and paw-jerk) were recorded for 60 min. Corticosterone, testosterone and estradiol serum levels were determined in blood obtained at the end of the experiment. BPA-prenatal treatment induced an increase in licking duration in females and in flexing duration in both sexes in the first half of the test (0-30 min after formalin injection). BPA-postnatal treatment induced a decrease in paw-jerk frequency in males and females during the second part of the test (30-60 min after formalin injection). Plasma concentrations of corticosterone, estradiol and testosterone did not differ significantly between groups. These results indicate that exposure to BPA modified the activity of neural pathways and/or centers involved in nociception and pain in a sex-related and exposure-related manner.