A systematic review and meta-analysis on the association between orthostatic hypotension and mild cognitive impairment and dementia in Parkinson's disease.

BACKGROUND: Cognitive impairment is a frequent disabling feature of Parkinson's disease (PD). Orthostatic hypotension (OH) is treatable and may be a risk factor for cognitive impairment. OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between OH with PD-associated minimal cognitive impairment (PD-MCI) and dementia (PDD) and assess the mitigating effects of potential confounding factors. METHODS: Observational studies published in English, Spanish, French, or Portuguese up to January 2022 were searched for in PubMed, EBSCO, and SciELO databases. The primary aim of this study was to revise the association between OH with PD-MCI and PDD. Alongside, we assessed OH as related to cognitive rating scales. Fixed and random models were fitted. Meta-regression was used to assess the mitigating effects of confounding variables. RESULTS: We identified 18 studies that reported OH association with PDD or PD-MCI, 15 of them reporting OH association with cognitive rating scales. OH was significantly associated with PDD/PD-MCI (OR, 95% CI: 3.31, 2.16-5.08; k = 18, n = 2251; p < 0.01). OH association with PDD (4.64, 2.68-8.02; k = 13, n = 1194; p < 0.01) was stronger than with PD-MCI (1.82, 0.92-3.58; k = 5, n = 1056; p = NS). The association between OH and PD-MCI/PDD was stronger in studies with a higher proportion of women and in those with a lower frequency of supine hypertension. Global cognition rating scale scores were lower in patients with OH (SMD, 95% CI: - 0.55, - 0.83/ - 0.26; k = 12, n = 1427; p < 0.01). CONCLUSIONS: Orthostatic hypotension shows as a significant risk factor for cognitive impairment in PD, especially in women and patients not suffering from hypertension.

Renal Damage During Continuous Versus Intermittent Treatment with Lithium.

The aim of this study was to evaluate renal damage in animals treated with lithium continuously versus intermittently. Rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months and two experimental groups, one of them fed ad libitum the same diet or the same diet supplemented with 60 mmol of lithium/kg diet every alternate week, for 3 months and the other fed ad libitum powered standard diet for one and a half month and the same diet supplemented with 60 mmol of lithium/kg diet for the last month and a half. Lithemias in experimental groups were within therapeutic range used in humans. At the end of the protocol, diuresis was higher in experimental groups compared to control group. There was no difference in serum creatinine and creatinine clearance. Both experimental groups showed hypertrophy, hyperplasia, and dilatation of cortical collecting tubules although dilatation was greater in continuous group. Longer studies are necessary to clarify the evolution of renal damage. Our preliminary study shows that histopathological damage associated with the use of lithium occurs during both continuous and intermittent treatment, but it seems to be somewhat greater in the continuous group.

Relación deltre hipotiroidismo subclínico y bocio con el origen del agua consumida por una población del conurbano bonaerense / Relationship of subclinical hypothyroidism and goiter with the origin of water consumed by a population of the Buenos Aires suburbs

El hipotiroidismo subclínico (HS), elevación de tirotrofina con hormonas tiroideas normales, junto al bocio, aumentó la frecuencia en las últimas décadas. Con el objetivo de relacionar la prevalencia de bocio y HS con el consumo de agua subterránea como factor de riesgo etiológico poblacional, se analizaron 879 historias clínicas de un centro médico de Glew, en el conurbano bonaerense Sur. Se estudió la población según edad (20-60 y 12-19 años) y tipo de agua consumida (potabilizada o napa subterránea). El agua subterránea fue consumida por el 70.5% del grupo de 20 a 60 años (n = 559, 79.9% mujeres) y por el 66.3% del grupo de 12 a 19 años (n = 57, 81.4% mujeres). En el grupo de 20 a 60 años la prevalencia de HS en consumidores de agua potabilizada y subterránea fue del 1% y 57.8% (p < 0.0001) y la de bocio de 3.8% y 38.9% (p < 0.0001), respectivamente; con un riesgo atribuible al agua subterránea de 57% para HS y 35% para bocio. En el grupo de 12 a 19 años, la prevalencia de HS fue 6.9% y 52.6% (p < 0.0001) y de bocio 13.8% y 77.2% para los grupos de agua potabilizada y subterránea, (p < 0.0001) respectivamente; con un riesgo atribuible al agua subterránea de 46% para HS y 61% para bocio. El análisis fisicoquímico mostró presencia de nitratos (entre 24 y 83 mg/l) en aguas de pozos y ausencia en agua potable. La prevalencia aumentada de HS y bocio podrían deberse a la acción disruptora tiroidea de los nitratos.

Subclinical hypothyroidism (SH), elevation of the level of thyrotrophin with normal thyroid hormones, along with goiter (glandular size > 25g), increased in recent decades. In order to relate the prevalence of goiter and SH with the consumption of groundwater, as a population etiological risk factor, we analyzed 879 clinical histories from a medical center in the city of Glew in the South Buenos Aires suburbs. The population was studied according to age (20 to 60 and 12 to 19 years) and type of water consumed (potable water or groundwater). Groundwater was consumed by 70.5% of the group from 20 to 60 years old (n = 559, 79.9% women) and by 66.3% of the group from 12 to 19 years old (n = 57, 81.4% women In the group of 20 to 60 years, the prevalence of SH in potable water and groundwater users was 1% and 57.8% (p < 0.0001) and the goiter rate of 3.8% and 38.9% (p < 0.0001) respectively; with an attributable risk to groundwater of 57% for HS, and 35% for goiter In the group of 12 to 19 years, the prevalence of SH was 6.9% and 52.6% (p < 0.0001) and goiter 13.8% and 77.2% for the water and groundwater groups (p>0.0001) respectively, with an attributable risk of 46% for HS y 61% for goiter. The physicochemical analysis showed the presence of nitrates in the range of 24 to 83 mg/l in groundwater and absence in potable water. The increased prevalence of HS and goiter could be due to the thyroid disrupting action of nitrates.

[Relationship of subclinical hypothyroidism and goiter with the origin of water consumed by a population of the Buenos Aires suburbs]. / Relación del hipotiroidismo subclínico y bocio con el origen del agua consumida por una población del conurbano bonaerense.

Subclinical hypothyroidism (SH), elevation of the level of thyrotrophin with normal thyroid hormones, along with goiter (glandular size > 25g), increased in recent decades. In order to relate the prevalence of goiter and SH with the consumption of groundwater, as a population etiological risk factor, we analyzed 879 clinical histories from a medical center in the city of Glew in the South Buenos Aires suburbs. The population was studied according to age (20 to 60 and 12 to 19 years) and type of water consumed (potable water or groundwater). Groundwater was consumed by 70.5% of the group from 20 to 60 years old (n = 559, 79.9% women) and by 66.3% of the group from 12 to 19 years old (n = 57, 81.4% women In the group of 20 to 60 years, the prevalence of SH in potable water and groundwater users was 1% and 57.8% (p < 0.0001) and the goiter rate of 3.8% and 38.9% (p < 0.0001) respectively; with an attributable risk to groundwater of 57% for HS, and 35% for goiter In the group of 12 to 19 years, the prevalence of SH was 6.9% and 52.6% (p < 0.0001) and goiter 13.8% and 77.2% for the water and groundwater groups (p > 0.0001) respectively, with an attributable risk of 46% for HS y 61% for goiter. The physicochemical analysis showed the presence of nitrates in the range of 24 to 83 mg/l in groundwater and absence in potable water. The increased prevalence of HS and goiter could be due to the thyroid disrupting action of nitrates.

Leptin inhibits the reproductive axis in adult male Syrian hamsters exposed to long and short photoperiod.

The aim of the study was to investigate the effects of acute leptin treatment of adult Syrian hamsters exposed to a long (LP, eugonadal males) and short photoperiod (SP, hypogonadal males). Animals were exposed to LP (L:D 14:10) or SP (L:D 10:14) for 10 weeks. Afterwards, both LP and SP hamsters were allocated to a control (SP-C, LP-C) or leptin-treated group (SP 3, SP 10, SP 30 or LP3, LP 10, LP 30). One hour before sacrifice, a single dose of leptin (3, 10 or 30 µg/kg) or vehicle was administered (i.p.) to the males. Testis weight, serum and pituitary luteinizing hormone (LH) concentrations, as well as the hypothalamic concentration of gonadotropin-releasing hormone (GnRH) were recorded. Histological analysis of the testis was performed and GnRH concentration in the culture medium of hypothalamic explants was examined. A dramatic regression of testicular weight and histological atrophy of seminiferous tubules, as well as a decrease in serum and pituitary LH concentrations were found in SP males. All doses of leptin significantly reduced serum LH levels and medium GnRH concentrations in both photoperiod groups. Pituitary LH and hypothalamic GnRH concentrations were not affected by leptin. In conclusion, we demonstrated that leptin inhibited the reproductive axis of Syrian male hamsters exposed to LP and SP and fed ad libitum.

Evidence of reproductive disruption associated with neuroendocrine changes induced by UV-B filters, phthalates and nonylphenol during sexual maturation in rats of both gender.

Endocrine disruptors (EDs) are exogenous substances or xenoestrogens natural or synthetic, capable of interacting with different systems and altering their normal hormonal regulation, being the reproductive system one of the most affected. EDs produce their effects not only by acting on nuclear steroid receptors, but also on membrane receptors, steroidal and non-steroidal synthetic enzymatic pathways and/or metabolism. The incorporation to the body depend on each EDs, which are liposoluble and easily deposited in the tissue; thus ensuring a prolonged accumulation and release, even when the exposure is not continuous. In addition to cross the placenta, EDs may act in the offspring during the reproductive system formation and maturation key stages and its regulatory mechanisms. The effects of EDs can be multiple, but most acts mediating estrogenic and/or antiandrogenic effect. Three groups of EDs are widely used: in plastics (phtalates), sunscreens (cinnamate and methylbenzylcamphor), and detergents (nonylphenol). In this paper we review the effects of the exposure to these environmental chemicals on the reproductive system and the possible mechanisms by which they occur, focusing in the hypothalamic-pituitary neuroendocrine mechanisms that regulate the reproductive system.

Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats.

Effect of leptin on LH levels and hypothalamic release of GnRH. Its relationship with the hypothalamic neurotransmitter amino acids system in adult male rats.

The objective of the present paper was to determine the effect of leptin on the reproductive axis in adult male rats, as well as the hypothalamic mechanisms involved in this effect. For this purpose, we studied the in vivo effect of leptin in adult male rats on serum LH levels, and the in vitro effect on hypothalamic GnRH and amino acid neurotrasmitter release. For in vivo experiments, animals were injected i.p. with leptin at a dose of 30, 100 and 300 microg/kg. In the in vitro experiments, hypothalamic samples were incubated for 60 min in Earle's medium with leptin: 10(-9), 10(-10) and 10(-12) M for GnRH determination, and 10(-10) M for amino acids evaluation. Finally, we studied the effect of the lowest effective leptin dose on plasma LH levels in peripubertal male rats to compare the effect between this group and adults. Leptin induces significant decreases of serum LH levels with the different studied doses (p < 0.01 vs. control) in adult male rats, while in peripubertal male rats, it induced a significant (p < 0.01 vs. control) increment in serum LH levels. On the other hand, in vitro leptin in adult male rats, significantly decreases GnRH release as well as the hypothalamic release of glutamate (GLU). In contrast, leptin increased the GABA release by this hypothalamus in these animals. These results indicate that leptin has an inhibitory effect on the GnRH-LH axis in adult male rats and this effect appears to be connected with an inhibition of hypothalamic release of GLU (the excitatory amino acid) and a stimulatory effect on GABA release (the inhibitory amino acid). On the other hand, in peripubertal male rats, leptin showed a stimulatory effect.

Effects of gabaergic and serotoninergic systems on hypothalamic content of catecholamines during sexual development in female rats.

OBJECTIVES: The aim of the present investigation was to determine whether the catecholaminergic system is involved in gabaergic and serotoninergic effects on gonadotrophin secretion during sexual development. To this end, we studied the effect of GABAergic and serotoninergic systems on hypothalamic catecholamine content at different stages of sexual development. METHODS: The effect of GABA A and GABA B agonists and 5-hydroxy-L-tryptophan on hypothalamic noradrenaline and dopamine content were determined in prepubertal (16 days old) and peripubertal (30 days old) rats. RESULTS: At 16 days of age GABA agonists did not modify hypothalamic noradrenaline content, whereas a significant decrease in catecholamine concentration was observed in peripubertal rats at 30 days of age. Similar changes were observed with GABA agonists administration on dopamine hypothalamic levels, i.e no effects at 15 days of age and a significant decrease at 30 days. The administration of 5-hydroxy-l-tryptophan (5-HTP) induced a decrease of hypothalamic concentration of noradrenaline and dopamine at both ages. CONCLUSION: Results indicate that the GABAergic system modifies the hypothalamic catecholamine content in peripubertal but not in prepubertal rats while serotonin has an inhibitory effect at both stages of sexual maturation. Even though both systems induce similar ontogenic modifications on the gonadotrophin axis (stimulatory effect in prepubertal and inhibitory action in peripubertal and adult rats) the present results appear to indicate that GABAergic and serotoninergic systems regulate gonadotrophin secretion by different hypothalamic mechanisms.

Effect of aproteic diet and fasting on insulin, pancreatic noradrenaline and luteinizing hormone. Changes after 24-hour refeeding.

OBJECTIVE AND DESIGN: the objective of this study performed in adult male rats was to determine the alteration in glycemic, insulin and gonadotrophin luteinizing hormone secretion, and noradrenaline pancreatic concentration caused by fasting (F) and aproteic diet (Ap) during 7 and 21 days respectively, as well as the recovery after 24-hour refeeding with control diet (Co). RESULTS: a significant decrease in glycemic levels was only achieved through fasting (F: 86 +/- 5.1 mg %), when compared with controls (Co: 107 +/- 5 mg %). In spite of the high levels of carbohydrates (89%) present in the aproteic diet, the animals fed with this diet showed no differences in glycemic levels (Ap: 120.3 +/- 12.2 mg %), compared with controls. As a result of fasting and aproteic diet, there was a significant decrease in insulin (F: 8.67 +/- 1.36; Ap: 5.7 +/- 0.67; Co: 31 +/- 3.4 uU/ml) and LH levels (F: 10.175 +/- 1.74; Ap: 13.7 +/- 4; Co: 29.83 +/- 4.91 ng/ml). The refed recovered insulin (FR: 50.57 +/- 6.63; ApR: 43.5 +/- 6.85 uU/ml), but not LH levels (FR: 14.25 +/- 3.54; ApR: 13.03 +/- 4.25 ng/ml). A significant increase was observed in the pancreatic noradrenaline concentration (P<0.001) of rats receiving aproteic diet (889.9 +/- 34.65 ng/mg tissue) and fasting during 7 days (827.5 +/- 55.7 ng/mg tissue), compared with controls (531.1 +/- 48.6 ng/mg tissue). CONCLUSIONS: fasting and aproteic diets altered gonadal and metabolic control. When returning to a normal nutritional condition, only the metabolic control, not the reproductive function, could be recovered in the first 24 hours of refeeding. Malnutrition-induced hypoinsulinemia would be caused by an increase in a specific noradrenergic tone.

Effects of aproteic diet on hypothalamic-pituitary- gonadal regulation in the male rat.

The effect of an aproteic diet (Ap) on the reproductive axis in young male rats was studied. Also the refeeding effect at different times after the aproteic diet was studied. The Ap diet was given during 21 days. In refeeding groups, the control diet was given during 2, 4 and 6 weeks after the aproteic diet. We studied the plasmatic testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. Also the hypothalamic GnRH concentration and in vitro hypothalamic GnRH secretion in basal and induced condition was studied. The total protein deficit produced significant reduction in body, testis, seminal vesicles and prostate weights. This was accompanied with decreased levels of plasmatic testosterone (P<0.02). In this aproteic group there was a significant reduction in LH (P<0.05) and FSH (P<0.05) plasmatic levels. Refeeding with control diet reversed this situation, producing significant increment in LH (P<0.05) and FSH levels (P<0.01) at the fourth and second weeks, respectively. The basal hypothalamic GnRH secretion did not differ from the control; nevertheless the induced secretion was significantly (P<0.05) greater in the aproteic group. Also the hypothalamic GnRH concentration was increased (P<0.05) in animals fed with the aproteic diet. The minor testis, prostate, and seminal vesicles" weight, and a decreased plasmatic testosterone in rats fed with an aproteic diet, are produced by a decrease in gonadotrophin secretion. This decrease in turn is caused by a reduction in GnRH secretion, since hypothalamic GnRH concentration is increased in rats fed with the aproteic group, and induced secretion is greater in this group. All these alterations produced by an aproteic diet are reversible, since-with contol diet refeeding-the gonadotrophin secretion returned at control levels.