Primary Dysmenorrhea: pathophysiology

The present study was conducted to investigate and analyze the recent and relevant studies about primary dysmenorrhea and its pathophysiology. Literature searches were performed electronically in PubMed, Medline, ISI, DOAJ, Springer, Embase. Web of Knowledge, DOAJ, Google Scholar and the Cochrane Library for original articles written in English and in Scielo, Lantidex, Imbiomed-L, Redalyc and Google Scholar for original articles written in Spanish. The searches included the key words (Mesh): menstruation, menstrual period, menstrual cycle, dysmenorrhea, primary dysmenorrhea, inflammatory substance and inflammatory markers. Publications from January 1980 to February 2021 were reviewed. Dysmenorrhea is the most common gynecologic condition experienced by menstruating women. It is characterized by crampy lower abdominal pain that can range widely in severity, and associated to others symptoms. Its overall impact often has significant medical and psychosocial implications. The hallmark of primary dysmenorrhea is painful menses in the absence of any associated macroscopic pathologic process, and it occurs in up to 50% of menstruating females and causes significant disruption in quality of life and absenteeism. An excessive or imbalanced amount of prostanoids and possibly eicosanoids released from the endometrium during menstruation have been mentioned as the main cause of primary dysmenorrhea. The uterus is induced to contract frequently and dysrhythmically, with increased basal tone and increased active pressure. Uterine hypercontractility, reduced uterine blood flow and increased peripheral nerve hypersensitivity induce pain. Diagnosis rests on a good history with negative pelvic evaluation findings. This narrative review investigated and analyzed the pathophysiology of primary dysmenorrhea and the implications of other chemical substances.

The results of sphincterometry in patients after sorgion treatment of extrasphintery anal fistula

More than 30% of patients with chronic paraproctitis have complex forms. They are most often complicated by external sphincter insufficiency due to deformation of the anal canal and scarring of the sphincters. The main principle of substantiation of surgical treatment of extrasphincteric pararectal fistulas is the individual choice of method in each particular patient. It is based on a comprehensive assessment of such factors as the etiology of the fistula, its distance from the edge of the anus, the relationship of the defect or fistula with the sphincter muscles apparatus, the severity of the scarring process, the functional state of the rectum. Aim. Evaluation of the functional state of the sphincter apparatus of the rectum in patients with extrasphincteric pararectal fistulas in the preoperative, early and late postoperative periods. Materials and methods. To determine the average indicators of anal sphincter function, basal tone and maximal compression force were measured using a sphincterometer "Sphinctometer STM-0164-SM" in 114 healthy individuals (68 men and 46 women) of different ages (16 to 80 years) who objectively had no signs of anal incontinence. In all patients, sphincterometry was preceded by a thorough proctological examination, and proctological pathology was excluded. Therefore, hemorrhoids or anal fissures, which lead to increased basal tone at rest, were excluded so as not to lead to falsified values. Results. Indicators of the maximum compression force in the early postoperative period, ie the compression force of the external anal sphincter, in both groups were significantly lower than preoperative and ranged from 55 to 154 mm Hg, respectively. and from 63 to 137 mm Hg. This can be explained by the presence of a granulating wound in the pararectal tissue, edema and partial injury of the external anal sphincter during surgery. In the late postoperative period, 6-12 months after surgery, the indicators of basal tone in both groups approached the preoperative indicators. In the main group, the study was performed in 22 patients. In these 22 patients, the tone of the internal anal sphincter did not differ significantly from the preoperative and ranged from 20 to 37 mm Hg. In the control group, in all 32 patients, the basal tone of the anal sphincter was significantly lower than before surgery - from 17 to 28 mm Hg. There were no clinical manifestations of incontinence at rest in either main or control groups. In the late postoperative period in both groups a decrease in the maximum compression force of the external anal sphincter was revealed. In the main group the maximum compression force of the external anal sphincter varied from 71 to 186 mm Hg, and in the control group from 77 to 135 mm Hg, respectively. Conclusion. Surgical treatment of patients with extrasphincteric pararectal fistulas significantly reduces the contractile function of the external anal sphincter in the postoperative period, regardless of the choice of surgery.

The calcium sensor synaptotagmin-1 is critical for phasic axonal dopamine release in the striatum and mesencephalon, but is dispensable for basic motor behaviors in mice

Midbrain dopamine (DA) neurons, a population of cells that are critical for motor control, motivated behaviors and cognition, release DA via an exocytotic mechanism from both their axonal terminals and their somatodendritic (STD) compartment. In Parkinson's disease (PD), it is striking that motor dysfunctions only become apparent after extensive loss of DA innervation. Although it has been hypothesized that this resilience is due to the ability of many motor behaviors to be sustained through a basal tone of DA and diffuse transmission, experimental evidence for this is limited. Here we conditionally deleted the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (cKODA mice) to abrogate most activity-dependent axonal DA release in the striatum and mesencephalon, leaving STD DA release intact. Strikingly, Syt1 cKODA mice showed intact performance in multiple unconditioned DA-dependent motor tasks, suggesting that activity-dependent DA release is dispensable for such basic motor functions. Basal extracellular levels of DA in the striatum were unchanged, suggesting that a basal tone of extracellular DA is sufficient to sustain basic movement. We also found multiple adaptations in the DA system of cKODA mice, similar to those happening at early stages of PD. Taken together, our findings reveal the striking resilience of DA-dependent motor functions in the context of a near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.

Arachnoid membrane as a source of sphingosine-1-phosphate that regulates mouse middle cerebral artery tone

Growing evidence indicates that perivascular tissue is critical to modulate vessel function. We hypothesized that the arachnoid membrane surrounding middle cerebral artery (MCA) regulates its function via sphingosine-1-phosphate (S1P)-induced vasoconstriction. The MCA from 3- to 9-month-old male and female wild-type (Oncine France 1 and C57BL/6) mice and sphingosine kinase 2 knockout (SphK2-/-) mice in the C57BL/6 background was mounted in pressure myographs with and without arachnoid membrane. Raman microspectroscopy and imaging were used for in situ detection of S1P. The presence of arachnoid tissue was associated with reduced external and lumen MCA diameters, and with an increase in basal tone regardless of sex and strain background. Strong S1P-positive signals were detected in the arachnoid surrounding the MCA wall in both mice models, as well as in a human post-mortem specimen. Selective S1P receptor 3 antagonist TY 52156 markedly reduced both MCA vasoconstriction induced by exogenous S1P and arachnoid-dependent basal tone increase. Compared to 3-month-old mice, the arachnoid-mediated contractile influence persisted in 9-month-old mice despite a decline in arachnoid S1P deposits. Genetic deletion of SphK2 decreased arachnoid S1P content and vasoconstriction. This is the first experimental evidence that arachnoid membrane regulates the MCA tone mediated by S1P.

Study of the constrictor properties of the neobladder under the influence of new chemical compounds in vivo experiment

The orthotopic ileocystoplasty is the most preferred urine derivation method for patients after removal of the bladder. The best quality of life, self-esteem, cosmetic appearance of one’s own body, and the possibility of physiological urination characterize the artificial bladder as the “gold standard” of urine derivation. There are a greater number of postoperative complications associated with the functionality of the neobladder, considering the complexity of orthotopic derivation of urine. The autocaturation is required in some patients day or night urinary incontinence, and in the other group, periodic urinary retention. Urinary retention is more common in women up to 43 % compared with 20 % in men, who need intermittent catheterization. The aim of investigation was to evaluate the possibility of pharmacological correction of contractile activity of mini-pigs neobladder in vivo, under the influence of new chemical compounds and the anticholinesterase drug nivalin. Materials and methods Experimental studies were performed on 21 female mini-pigs, with an average age of 6 to 14 months. The duration of the experiment was 12 months. Performing of enterocystometry in experimental animals is possible only under anesthesia and, accordingly, only part of the urodynamic parameters can be obtained. Results. The obtained results of in vivo experimental studies demonstrated the constrictor activity of the studied new chemical compounds. Compound I in comparison with the control group statistically significantly increased basal tone by 62.09 %, the amplitude of contractions by 37.34 %, and the duration of contractions by 35.71 %. The new chemical compound II, in comparison with the control group, showed less pronounced results of constrictor activity, so the basal tone statistically significantly increased by 38.86 %, and the amplitude of contractions by 15.0 %. Conclusion. Thus, under the influence of new chemical compounds in the conditions of an experimental artificial bladder, constrictor properties are proved, which require further research and study. In turn, cholinomimetic nivalin has prospects for use in urology, in particular in patients with hypoactive forms of artificial and neurogenic bladder.

Do Mistletoe (Viscum album L.) Lectins Influence Isometric Contraction of Non-diseased Human Mesenteric Arteries ex vivo?

Mistletoe (Viscum album L., VA) lectins (MLs) are plant lectins with potent anticancer activity. Although wide use of VA extracts in curing cancer, the effects of purified MLs on human vasculature in term of possible side effect of the lectin has not yet been reported. The present study was aimed to investigate isometric contractions of isolated human mesenteric arteries during MLs application. The contractile response of arteries was studied using Mulvany-Halpern myograph and the isometric contractions under MLs’ treatment were examined in artery segments with either intact endothelium or after endothelium removal. Furthermore, the effect of the lectin was assessed in arterial preparations in basal tension, in arteries precontracted with 42 mM KCl as a depolarizing stimulus or endothelin-1 (ET-1) as a potent receptor-operated agonist of vascular smooth muscle contraction. The results showed that MLs (1 to 100 nM) failed to affect the high K+-induced contractions of both endothelium-intact and endothelium-denuded arteries. The contractions of tissue preparations without endothelium in basal tone or after ET-1 (1 nM) treatment were also not affected by the application of MLs. The observed mild effect of MLs on the contractility of human vasculature may potentially be beneficial with MLs-based anticancer therapy without vascular side effects.