EFFECT OF HORMONAL CONTRACEPTION ON DEPRESSION IN WOMEN.

Oral contraceptives are the most frequently chosen method of preventing pregnancy in Poland. Mood changes are one of the most common reasons why young women quit therapy. Depression is a severe disorder that affects millions of people around the world. Some long-term studies suggest an increased relative risk of antidepressant use during contraceptive use compared to non-users. Scientists note an increased risk of suicide as well. Other researchers suggest that there is insufficient evidence to support these findings. Some indicate strong correlation between most hormonal contraceptives and following usage of antidepressant drugs in female adolescents. There is still no consensus in the scientific community. Analyzes of many studies provide ambiguous information. Large-scale studies with properly selected test groups and particular therapies taken into consideration are required in order to accurately assess the risk of depression and mood disorders. In this article, we try to present different approaches to the subject of effects of various types of hormonal contraception methods on depression in women.

Effects of 17-ß-estradiol released from shape-memory terpolymer rods on sciatic nerve regeneration after injury and repair with chitosan nerve conduit in female rats.

The aim of this study was to assess 17-ß-estradiol (E2) influence on sciatic nerve regeneration after injury followed by a repair with chitosan conduit in ovariectomized female rats. The study was performed in 2 groups (n = 16) of rats: OVChit - after excision of a fragment of the sciatic nerve, a chitosan conduit was implanted; OVChitE10 group - additionally to chitosan conduit, shape-memory terpolymer rods based on poly(L-lactide-co-glycolide- co-trimethylene carbonate) releasing 17-ß-estradiol for 20 weeks were implanted. The mean number of regenerating axons and mean fiber area were significantly greater in 17-ß-estradiol-treated animals. In this group, the infiltrate of leukocytes was diminished. The presence of 17-ß-estradiol receptors alpha and beta in motoneurons in the spinal cord were discovered. This may indicate the location where 17-ß-estradiol affects the regeneration of the injured nerve. Estradiol released from the terpolymer rods for 20 weeks could enhance, to some extent, sciatic nerve regeneration after injury, and diminish the inflammatory reaction. In the future, 17-ß-estradiol entrapped in terpolymer rods could be used in the repair of injured peripheral nerves, but there is a need for further studies.

TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients.

Loss of pancreatic ß-cell is a critical factor in the pathogenesis of type 1 diabetes and it also occurs in type 2. TXNIP (thioredoxin - interacting protein), also known as vitamin D3-upregulated protein 1, or thioredoxin-binding-protein-2, regulates this process and modulates cellular redox balance. TXNIP is localized primarily in the nucleus, but under oxidative stress it moves to mitochondria, where it interacts with mitochondrial thioredoxin 2. Overexpression of TXNIP induced by hyperglycaemia is typical for diabetes and insulin resistance and leads to apoptosis of pancreatic ß-cell, cardiomyopathy, metabolic disorders and multiple harmful effects. It activates NLRP3 inflamasomme and IL-1ß, a cytokine involved in type 2 diabetes and insulin resistance. TXNIP influences peroxisome proliferator-activated receptor alpha transcriptional activity, expression of glucose transporter-1, nitric oxide production in endothelium and insulin production in ß-cells. TXNIP overexpression leads to diabetic retinopathy, nephropathy, atherosclerosis, it occurs in cancers and autoimmune diseases, while its deficiency protects ß cells. Reduction of TXNIP is an important target in diabetes treatment. In this mechanism insulin, metformin and inhibitors of dipeptydylopeptydase IV are involved. It has been observed that calcium channel blockers (CCB) used in hypertension also inhibit TXNIP expression in cardiomyocytes. L-type channels identification in pancreatic ß-cells revealed that CCB inhibit TXNIP expression also in ß-cells. For the first time, verapamil was distinguished as an agent that not only inhibits TXNIP expression in pancreatic ß-cells, but also enhances ß cell survival and function, and possibly prevents diabetes.

The influence of hypertension, diabetes, lipid disorders and the presence of the APOE4 allele on the cognitive functions of patients over 65 years of age.

Diabetes mellitus (DM) and hypertension (HA) are common diseases in the population of people over 65 years of age. Many studies show the impact of the long-lasting decompensation of these chronic diseases, often diagnosed in middle age, on the cognitive functioning of elderly patients. RESULTS: There is almost 30% prevalence of cognitive impairment among patients diagnosed with arterial hypertension. Possible explanation includes intensification of inflammatory processes in the central nervous system, influence on cerebral blood flow and acceleration of atherosclerosis. Another analyzed factor is the presence of diabetes. DM impacts the development of Alzheimer's disease. The inflammatory processes are intensified by advanced glycation products promoting atherosclerotic changes in blood vessels. In addition to that, the presence of hypoglycemic episodes significantly increases the risk of dementia. Moreover, approximately 78% of adult diabetic patients are also diagnosed with arterial hypertension, resulting in the coexistence of these CNS damaging mechanisms. The effect of elevated total cholesterol concentration on cognitive performance is still under debate and more research is needed. The role of the presence of ApoE4 in the development of cognitive dysfunctions, including Alzheimer's disease is emphasized. CONCLUSIONS: In daily medical practice, extraordinary attention should be paid to control of chronic diseases of the patient, especially in the middle age. It improves cognitive functioning, possibly extending the quality-adjusted life year expectancy.

[Potential application of maraviroc in the therapy of neuropathic pain]. / Potencjalne zastosowanie marawiroku w terapii bólu neuropatycznego.

According to International Association for the Study of Pain (IASP) neuropathic pain is defined as a pain caused by a lesion or disease of the somatosensory nervous system. In general population 7-8% adults suffer from chronic pain with neuropathic characteristic. The most common causes include: lumbar radiculopathy, postherpetic neuropathy, HIV infection, autoimmune diseases (multiple sclerosis), metabolic diseases (diabetic neuropathy), stroke or spinal cord injury. Current pharmacotherapy of neuropathic pain has insufficient effectiveness, so comprehension of neuropathic pain mechanism is necessary for research of new therapeutic methods. In the study we verify the analgesic effect of maraviroc (antagonist of the chemokine receptor - CCR5) and its potential role in the treatment of neuropathic pain. In the study we focused on dependency between opioid and chemokine receptors, because of similar structure between this receptors occurs cross-desensitization phenomenon. Chemokine antagonist maraviroc belongs to a group of entry inhibitors, antiretroviral drug. It enhances analgesic properties of opioids by inhibition of crossdesensitization of opioid's receptor. Application of maraviroc with morphine can reduce effective dosage of morphine 2,3 fold. Moreover, research show that prophylactic administration of maraviroc without opioid analgesics suppresses development of neuropathic pain symptoms. It has influence on glial phenotype, decreases secretion of proinflammatory cytokines and increases anti-inflammatory cytokine secretion. Furthermore it decreases expression of chemikine receptor mRNA and chemikine ligand's secreted by microglia and astrocytes as a result of nerve injury. We conclude that maraviroc has immunomodulatory properties, potentiates opioid analgesics effect, and can be used in neuropathic pain therapy as a potential co-analgesic.

The neuroprotective effect of N-acetylcysteine in spinal cord-injured rats.

BACKGROUND: Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma. OBJECTIVES: The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats. MATERIAL AND METHODS: A total of 20 male Wistar C rats were subjected to SCI and divided into control and experimental groups. In the control group (n = 10) trepanation and SCI by means of a pressure impactor was performed without any therapy. In the study group (n = 10), 1 dose of NAC was applied intraperitoneally (150 mg/kg b.w.) immediately after SCI, and another one after 24 h. The functional outcome on the Basso-Beattie-Bresnahan (BBB) scale and sciatic functional index (SFI) and morphological features of regeneration were analyzed during a 12-week follow-up. The spinal cords and brains were collected 12 weeks after SCI for histopathological and immunohistochemical analyses. RESULTS: The rats treated with NAC presented some improvement in locomotor activity and spinal cord morphology when compared to the control group. Namely, the hind paw angle of rotation was significantly lower in the NAC group than in the control group. No differences were observed between the control and study groups in terms of interlimb coordination. The area of the main lesion was only slightly decreased in the NAC group as compared to the control group. The length of lesions in the injured spinal cord in the NAC group was diminished in comparison to the control group. The number of FG-positive cells was higher in the NAC group than in the control group. CONCLUSIONS: The study showed that the neuroprotective activity of NAC had limited positive influence on the regeneration of the isolated SCI in rats.

Stent-Assisted Endovascular Treatment of Anterior Communicating Artery Aneurysms - Literature Review.

The anterior cerebral artery is a common location of intracranial aneurysms. The standard coil embolization technique is limited by its inability to occlude wide-neck aneurysms. Stent deployment across the aneurysm neck supports the coil mass inside the aneurysmal sac, and furthermore, has an effect on local hemodynamic and biologic changes. In this article, various management strategies and techniques as well as angiographic outcomes and complications related to stent-assisted endovascular treatment of anterior communicating artery aneurysms are presented. This treatment method is safe and associated with low morbidity and mortality rates.

Poly(D,L-Lactide-Co-Glycolide) Tubes With Multifilament Chitosan Yarn or Chitosan Sponge Core in Nerve Regeneration.

PURPOSE: The influence of different kinds of nerve guidance conduits on regeneration of totally transected rat sciatic nerves through a 7-mm gap was examined. MATERIALS AND METHODS: Five different types of conduits made of chitosan and poly(D,L-lactide-co-glycolide) (PLGA) were constructed and tested in vivo. We divided 50 animals into equal groups of 10, with a different type of conduit implanted in each group: chitosan sponge core with an average molecular mass of polymer (Mv) of 287 kDa with 7 channels in a PLGA sleeve, chitosan sponge core with an Mv of 423 kDa with 7 channels in a PLGA sleeve, chitosan sponge core (Mv, 423 kDa) with 13 channels in a PLGA sleeve, chitosan multifilament yarn in a PLGA sleeve, and a PLGA sleeve only. Seven weeks after the operation, we examined the distance covered by regenerating nerve fibers, growing of nerves into the conduit's core, and intensity and type of inflammatory reaction in the conduit, as well as autotomy behavior (reflecting neuropathic pain intensity) in the animals. RESULTS: Two types of conduits were allowing nerve outgrowth through the gap with minor autotomy and minor inflammatory reactions. These were the conduits with chitosan multifilament yarn in a PLGA sleeve and the conduits with 13-channel microcrystalline chitosan sponge in a PLGA sleeve. CONCLUSIONS: The type of chitosan used to build the nerve guidance conduit influences the intensity and character of inflammatory reaction present during nerve regeneration, which in turn affects the distance crossed by regenerating nerve fibers, growing of the nerve fibers into the conduit's core, and the intensity of autotomy in the animals.

Sciatic nerve regeneration in rats subjected to ketogenic diet.

OBJECTIVES: Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. METHODS: Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. RESULTS: Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. DISCUSSION: Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat.

The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150-300 µT, 80-150 µT, 20-80 µT; frequency 40 Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1 d/20 min., 5 d/week, for 28 d. Behavioural tests assessing the intensity of allodynia and sensitivity to mechanical and thermal stimuli were conducted 1 d prior to surgery and 3, 7, 14, 21 and 28 d after the surgery. The extent of autotomy was examined. Histological and immunohistochemical analysis was performed. The use of extremely low-frequency magnetic fields of minimal induction values (20-80 µT/40 Hz) decreased pain in rats after nerve transection. The nociceptive sensitivity of healthy rats was not changed following the exposition to the spatial magnetic field of the low frequency. The results of histological and immunohistochemical investigations confirm those findings. Our results indicate that extremely low-frequency magnetic field may be useful in the neuropathic pain therapy.

Reduction of post-traumatic neuroma and epineural scar formation in rat sciatic nerve by application of microcrystallic chitosan.

Injury of peripheral nerve is associated with the development of post-traumatic neuroma at the end of the proximal stump, often being the origin of neuropathic pain. This type of pain is therapy-resistant and therefore extremely nagging for patients. We examined the influence of the microcrystallic chitosan gel applied to the proximal stump of totally transected sciatic nerve on the neuroma formation and neuropathic pain development in rats. In 14 rats, right sciatic nerve was transected and the distal stump was removed to avoid spontaneous rejoining. In the chitosan (experimental) group (n = 7), the proximal stump was covered with a thin layer of the microcrystallic chitosan gel. In control animals (n = 7), the cut nerve was left unsecured. Autotomy, an animal model of neuropathic pain, was monitored daily for 20 weeks following surgery. Then, the animals were perfused transcardially and the proximal stumps of sciatic nerves were dissected and subjected to histologic evaluation. The presence, size, and characteristics of neuromas as well as extraneural fibrosis were examined. In chitosan group, the incidence and the size of the neuroma were markedly reduced, as compared with the control group; however, there was no difference in autotomy behavior between groups. In addition, extraneural fibrosis was significantly reduced in chitosan group when compared to the control group. The results demonstrate beneficial influence of microcrystallic chitosan applied to the site of nerve transection on the development of post-traumatic neuroma and reduction of extraneural fibrosis, however without reduction of neuropathic pain.

[The use of chitosan to facilitate nerve regeneration]. / Zastosowanie chitozanu we wspomaganiu regeneracji nerwów.

Chitosan, a biopolymer derived from chitin, biocompatible, biodegradable and antibacterial, has many medical applications. For more than a decade scientists have been studying the influence of chitosan on facilitating regeneration of peripheral nerves and neurons of central nervous system in animal models. First clinical attempts have also commenced. Because of many modifications that can be applied to chitosan, e.g. combining with drugs, growth factors, nerve stem cells, and connecting with other biopolymers, this material seems very promising. In this article the authors present the results of worldwide performed experiments concerning the use of chitosan to facilitate nerve regeneration. This work contains description of experiments which used chitosan as: cell culture medium, drug carrier, chitosan tunnels, sponge, fibers, films, multichannel and multicomponent chitosan conduits, chitooligosaccharides and the influence of all chitosan forms listed above on regenerating neurons.

17beta-estradiol and predegenerated nerve graft effect on hippocampal neurogenesis in adult female rats.

OBJECTIVES: The aim of present work was to examine estrogen influence on neurogenesis in the model of predegenerated peripheral nerve grafts implantation into the rat hippocampal dentate gyrus. METHODS: Experiment was carried out on female rats divided into three experimental groups: NO - non-ovariectomized, OV - ovariectomized and E - heterogeneous group with various 17-beta-estradiol substitution after ovariectomy. Proliferating cells were labeled with BrdU. Brains were subjected to immunohistochemical procedures to visualize nestin, GFAP and estrogen receptors (ERalpha and ERbeta). RESULTS: Proliferation rate was highest in E groups with estrogen levels resembling that in proestrus phase. Ovariectomy resulted in higher than in NO group number of new neurons, while high hyperestrogenemia worsened the results. The proportions of nestin-labeled cells correlated in similar way with different hormonal state. We found also distinct co-localization of nestin and GFAP in E group (proestrus). It may suggest the presence of radial glia, a potential source of new neurons in adult mammals. Nerve graft induced ERalpha expression at the site of injury in all groups. Distribution of ERbeta in hippocampus was estradiol-dose-dependent and correlated with cell proliferation. CONCLUSION: In our model, 17-beta-estradiol and predegenerated nerve graft implantation had synergistic effect on hippocampal neurogenesis.