Sexual dysfunction therapeutic approaches in patients with multiple sclerosis: a systematic review.

OBJECTIVE: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS are spasticity, pain, vesico-urethral disorders, cognitive impairments, chronic fatigue and sexual dysfunction. This review aims to explore the possible therapeutic options for managing sexual dysfunction in people with MS (PwMS). METHOD: A thorough search of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 up to 01/01/2022. The results were screened by the authors in pairs. RESULTS: The search identified 36 records. After screening, 9 records met the inclusion-exclusion criteria and were assessed. The pharmacological approaches investigated the effectiveness of sildenafil, tadalafil and onabotulinumtoxinA. Of the interventional studies the non-pharmacological investigated, the effectiveness of aquatic exercises, the application of pelvic floor exercises,the combination of pelvic floor exercises and mindfulness technique, the combination of pelvic floor exercises and electro muscular stimulation with electromyograph biofeedback, the application of yoga techniques and the efficacy of assistive devices like the clitoral vacuum suction device and the vibration device. CONCLUSION: The management of sexual dysfunction in PwMS needs to be further investigated. A team of healthcare professionals should be involved in the management of SD in order to address not only the primary (MS-related) SD symptoms but the secondary and tertiary as well. The main limitations that were identified in the existing literature were related to MS disease features, sample characteristics and evaluation tools and batteries.

Acute effects of coffee consumption on self-reported gastrointestinal symptoms, blood pressure and stress indices in healthy individuals.

BACKGROUND: It has been suggested that coffee may affect the gut-brain axis with conflicting outcomes. Moreover, there is insufficient evidence to determine whether the type or temperature of coffee consumed will have a different impact on the gut-brain axis. The purpose of this study was to investigate the effects of acute coffee consumption on the following: 1. self-reported GI symptoms and salivary gastrin, 2. stress indices [salivary cortisol and alpha-amylase (sAA)] and psychometric measures, and 3. blood pressure (BP), in healthy, daily coffee consuming individuals in non-stressful conditions. METHODS: This was a randomized, double blind, crossover clinical trial, in which 40 healthy individuals (20 men, 20 women), 20-55 years of age, randomly consumed four 200 ml coffee beverages containing 160 mg caffeine (hot and cold instant coffee, cold espresso, hot filtered coffee), 1 week apart. Salivary samples and psychometric questionnaires were collected at baseline and post-coffee consumption at 15,30, and 60 min for salivary gastrin and sAA measurements and at 60,120, and 180 min for cortisol measurements. BP was measured at beginning and end of each intervention. ClinicalTrials.gov ID: NCT02253628 RESULTS: Coffee consumption significantly increased sAA activity (P = 0.041), with significant differences only between cold instant and filter coffee at 15 and 30 min post-consumption (P < 0.05). Coffee temporarily increased salivary gastrin, without differences between coffee types. Coffee did not affect salivary cortisol or self-reported anxiety levels. Coffee consumption significantly increased BP, within the healthy physiological levels, in a gender specific manner at the end of the experimental periods, without differences between coffee types. CONCLUSION: Acute coffee consumption in non-stressful conditions activated sAA and BP but not salivary cortisol, indicating activation of the sympathetic nervous system. Post-coffee sAA increase without a concomitant cortisol increase may also indicate that coffee may have some anti-stress properties.

Inhibition of Na(+),K(+)-ATPase in the hypothalamus, pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism.

Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na(+),K(+)-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions' AChE and Mg(2+)-ATPase were recorded. The observed Na(+),K(+)-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na(+),K(+)-ATPase activity as a consistent neurochemical marker within the context of a systematic comparative study of existing (and novel) simulation approaches to congenital and early age hypothyroidism.

Experimentally-induced Wernicke's encephalopathy modifies crucial rat brain parameters: the importance of Na+, K+ -ATPase and a potentially neuroprotective role for antioxidant supplementation.

Wernicke's encephalopathy (WE) is a serious neuropsychiatric syndrome caused by chronic alcoholism and thiamine (T) deficiency. Our aim was to shed more light on the pathophysiology of WE, by introducing a modified in vivo experimental model of WE and by focusing on changes provoked in the total antioxidant status (TAS) and three crucial brain enzyme activities in adult rats. Rats were placed on ethanol (EtOH) consumption (20 % v/v) for a total of 5 weeks. By the end of the third week, rats were fed a T-deficient diet (TDD) and were treated with pyrithiamine (PT; 0.25 mg/kg) for the remaining 2 weeks. Following the induction of WE symptomatology, rats were treated with three consecutive (every 8 h) injections of saline or T (100 mg/kg) and were sacrificed. Brain homogenates were generated and used for spectrophotometrical evaluation of TAS and enzymatic activities. Additionally, in vitro experiments were conducted on brain homogenates or pure enzymes incubated with T or neuromodulatory antioxidants. Pre-exposure to EtOH provided a successful protocol modification that did not affect the expected time of WE symptomatology onset. Administration of T ameliorated this symptomatology. WE provoked oxidative stress that was partially limited by T administration, while T itself also caused oxidative stress to a smaller extent. Brain acetylcholinesterase (AChE) was found inhibited by WE and was further inhibited by T administration. In vitro experiments demonstrated a potential neuroprotective role for L-carnitine (Carn). Brain sodium-potassium adenosine triphosphatase (Na(+),K(+)-ATPase) activity was found increased in WE and was reduced to control levels by in vivo T administration; this increase was also evident in groups exposed to PT or to TDD, but not to EtOH. In vitro experiments demonstrated a potential neuroprotective role for this Na(+),K(+)-ATPase stimulation through T or L-cysteine (Cys) administration. Brain magnesium adenosine triphosphatase (Mg(2+)-ATPase) activity was found decreased by prolonged exposure to EtOH, but was not affected by the experimental induction of WE. Our data suggest that T administration inhibits AChE, which is also found inhibited in WE. Moreover, increased brain Na(+),K(+)-ATPase activity could be a marker of T deficiency in WE, while combined T and antioxidant co-supplementation of Cys and/or Carn could be neuroprotective in terms of restoring the examined crucial brain enzyme activities to control levels.

Short-term exposure to nickel alters the adult rat brain antioxidant status and the activities of crucial membrane-bound enzymes: neuroprotection by L-cysteine.

Nickel (Ni) is an environmental pollutant towards which human exposure can be both occupational (mainly through inhalation) and dietary (through water and food chain-induced bioaccumulation). The aim of this study was to investigate the effects of short-term Ni-administration (as NiCl(2), 13 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase, and Mg(2+)-ATPase; in addition, the potential effect of the co-administration of the antioxidant L-cysteine (Cys, 7 mg/kg) on the above parameters was studied. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Ni), C (Cys), and D (Ni and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above-mentioned parameters were measured spectrophotometrically. Rats treated with Ni exhibited a significant reduction in brain TAS (-47%, p < 0.001, BvsA) that was efficiently limited by the co-administration of Cys (-4%, p > 0.05, DvsA; +83%, p < 0.001, DvsB), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Ni (+30%, p < 0.001, BvsA) and Cys (+62%, p < 0.001, CvsA), while it tended to adjust to control levels by the co-administration of Ni and Cys (+13%, p < 0.001, DvsA; -13%, p < 0.001, DvsB). The activity of rat brain Na(+),K(+)-ATPase was significantly decreased by Ni-administration (-49%, p < 0.001, BvsA), while Cys supplementation could not reverse this decrease (-44%, p < 0.001, DvsA). The activity of Mg(2+)-ATPase was not affected by Ni-administration (-3%, p > 0.05, BvsA), but was significantly reduced when combined with Cys administration (-17%, p < 0.001, DvsA). The above findings suggest that Ni short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed to control levels by Cys co-administration; Cys could thus be considered (for future applications) as a potential neuroprotective agent against chronic exposure to Ni. The activity of Na(+),K(+)-ATPase that was inhibited by Ni, could not be reversed by Cys co-administration. The matter requires further investigation in order to fully elucidate the spectrum of the neurotoxic effects of Ni.