Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

Polarity Based Model for Guiding Medical School Strategy During Crisis - A Cross Sectional Qualitative Study.

BACKGROUND: Crises in academia can best be dealt with as a polarity that needs to be leveraged rather than a problem that needs to be solved. This work aimed at utilizing the Polarity Approach for Continuity and Transformation (PACT)™ to establish a guide for medical schools during times of crisis to minimize the effect of crisis-driven decisions on strategic growth. SUBJECTS AND METHODS: A qualitative study following the 5-Steps of the PACT process was conducted. A virtual mapping session was held with 108 medical educators from 22 countries to determine the upsides and downsides of strategic orientation and crisis management subsequently. RESULTS: Four polarity maps were generated identifying four tension areas; University reputation, mission, teams, and individuals followed by a 72-item assessment and another mapping session to map the warning signs and action steps. A comparison between private school scores and the whole cohort of respondents showed that private schools had the least problems in team-oriented work. CONCLUSION: This study highlighted the importance of taking measures to communicate the mission and supporting team functions inside universities either by enhancing resources or utilizing time and effort-saving strategies.

Investigating miRNA-661 and ATG4-B mRNA expression as potential biomarkers for hepatocellular carcinoma.

AIM: We aimed to examine the statistical association between serum expression of miRNA 661 (miR-661) and ATG-4B mRNA and hepatocellular carcinoma (HCC) based on in silico data analysis followed by clinical validation. PATIENTS & METHODS: Quantitative reverse-transcriptase real-time PCR was used to examine the expression of miR-661 and ATG-4B mRNA in the sera of HCC patients versus control. RESULTS: The expression of miR-661 and ATG-4B mRNA was positive in 97.14 and 77.14%, respectively, in HCC patients. The survival analysis showed that ATG-4B mRNA was an independent prognostic factor. CONCLUSION: Our data are the first report of its kind regarding the considerable clinical significance of miR-661 and ATG-4B mRNA in HCC patients.

Stop eating plastic, molecular signaling of bisphenol A in breast cancer.

Breast cancer is the second most common fatal cancer in women. Developing a breast cancer is a multi-factorial and hormonal-dependent process, which may be triggered by many risk factors. An endocrine disrupting substance known as bisphenol A (BPA), that is used greatly in the manufacture of plastic products, was suggested as a possible risk factor for developing breast cancer. BPA has a strong binding affinity to non-classical membrane estrogen receptors like estrogen-related and G protein-coupled (GPER) receptors. Based on animal and in vitro studies, results showed a link between BPA exposure and increased incidence of breast cancer. BPA has the ability to alter multiple molecular pathways in cells namely, G protein-coupled receptor (GPER) pathway, estrogen-related receptor gamma (ERRγ) pathway, HOXB9 (homeobox-containing gene) pathway, bone morphogenetic protein 2 (BMP2) and (BMP4), immunoregulatory cytokine disturbance in the mammary gland, EGFR-STAT3 pathway, FOXA1 in ER-breast cancer cells, enhancer of zeste homolog 2 (EZH2), and epigenetic changes. Thus, the aforementioned alterations cause undesired gene stimulation or repression that increase risk of developing breast cancer. So, restricting exposure to BPA should be considered to aid in lowering the risk of developing breast cancer.

Prenatal Exposure to Endocrine Disruptors and Reprogramming of Adipogenesis: An Early-Life Risk Factor for Childhood Obesity.

Obesity is a global health problem. It is characterized by excess adipose tissue that results from either increase in the number of adipocytes or increase in adipocytes size. Adipocyte differentiation is a highly regulated process that involves the activation of several transcription factors culminating in the removal of adipocytes from the cell cycle and induction of highly specific proteins. Several other factors, including hormones, genes, and epigenetics, are among the most important triggers of the differentiation process. Although the main contributing factors to obesity are high caloric intake, a sedentary lifestyle, and genetic predisposition, strong evidence supports a role for life exposure to environmental pollutants. Endocrine-disrupting chemicals are exogenous, both natural and man-made, chemicals that disrupt the body signaling processes, thus interfering with the endocrine system. Several studies have shown that prenatal exposure to endocrine disruptors modulates the mechanisms, by which multipotent mesenchymal stem cells differentiate into adipocytes. This review discusses adipocytes differentiation and highlights the possible mechanisms of prenatal exposure to endocrine disruptors in reprogramming of adipogenesis and induction of obesity later in life. Therefore, this review provides knowledge that reduction of early life exposure to these chemicals could open the door for new strategies in the prevention of obesity, especially during childhood.

A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer.

In metastatic breast cancer (MBC), the conventional doxorubicin (DOX) has various problems due to lack of selectivity with subsequent therapeutic failure and adverse effects. DOX- induced cardiotoxicity is a major problem that necessitates the presence of new forms to decrease the risk of associated morbidity. Nanoparticles (NPs) are considered an important approach to selectively increase drug accumulation inside tumor cells and thus decreasing the associated side effects. Tumor cells develop resistance to chemotherapeutic agents through multiple mechanisms, one of which is over expression of efflux transporters. Various NPs have been investigated to overcome efflux mediated resistance. To date, only liposomal doxorubicin (LD) and pegylated liposomal doxorubicin (PLD) have entered phase II and III clinical trials and FDA- approved for clinical use in MBC. This review addresses the effects of LD and PLD on the hematological and palmar-plantar erythrodysesthesia (PPE) in anthracycline naïve and pretreated MBC patients. For evidence, studies to be included in this review were identified through PubMed, Cochrane and Google scholar databases. The results derived from: four phase III clinical trials that compared LD with the conventional DOX in naïve MBC patients, and ten non-comparative clinical trials investigated LD and PLD as monotherapy or combination in pretreated MBC. This work confirmed the cardiac tolerability profile of LD and PLD versus DOX, while hematological and skin toxicities were more common. Other DOX-NPs in preclinical trials were discussed in a chronological order. Finally, the modern preclinical development framework for DOX includes exosomal DOX (exo-DOX). Exosomal NPs are non-toxic, non-immunogenic, and can be engineered to have high cargo loading capacity and targeting specificity. These NPs have not been investigated clinically. Our study shows that the full clinical potentiality of DOX-NPs remains to be addressed to move the field forward.

Role of the rectosigmoidal junction in fecal continence: concept of the primary continent mechanism.

HYPOTHESIS: At mass contraction of the descending colon, the colonic contents stop at the sigmoid colon (SC) and do not pass directly to the rectum. We investigated the hypothesis that a continent mechanism seems to exist at the rectosigmoidal junction (RSJ), preventing the direct passage of stools from the descending colon to the rectum. METHODS: The SC in 16 healthy volunteers (mean +/- SD age, 38.6 +/- 10.2 years; 9 men and 7 women) was distended with an isotonic sodium chloride solution-filled balloon, and the pressure response of the RSJ and the rectum was recorded at rapid and gradual filling of the balloon. The test was repeated after the SC and RSJ were anesthetized separately. RESULTS: Rapid SC balloon distension with a mean +/- SD of 52.1 +/- 3.6 mL of isotonic sodium chloride solution effected an RSJ pressure increase to a mean +/- SD of 67.8 +/- 18.4 cm H(2)O (P<.01) with no rectal pressure response (P>.05). Slow SC filling produced a progressive increase in RSJ pressure but no rectal pressure change. At a mean +/- SD SC distending volume of 86.3 +/- 4.1 mL, the RSJ pressure decreased to 9.6 +/- 2.8 (P<.01), and the balloon was dispelled to the rectum; rectal pressure increased (P<.001), and the balloon was expelled to the exterior. The RSJ pressure did not respond to distension of the anesthetized SC. CONCLUSIONS: Contraction of the RSJ at rapid SC distension with big volumes implies a reflex relationship that we call the RSJ guarding reflex. This reflex seems to prevent the descending colon contents from passing directly to the rectum. It is considered the first continent reflex and may serve as an investigative tool in the study of fecal incontinence.

Functional activity of the rectum: A conduit organ or a storage organ or both?

AIM: To investigate whether the degree of rectal distension could define the rectum functions as a conduit or reservoir. METHODS: Response of the rectal and anal pressure to 2 types of rectal balloon distension, rapid voluminous and slow gradual distention, was recorded in 21 healthy volunteers (12 men, 9 women, age 41.7 +/- 10.6 years). The test was repeated with sphincteric squeeze on urgent sensation. RESULTS: Rapid voluminous rectal distension resulted in a significant rectal pressure increase (P < 0.001), an anal pressure decline (P < 0.05) and balloon expulsion. The subjects felt urgent sensation but did not feel the 1st rectal sensation. On urgent sensation, anal squeeze caused a significant rectal pressure decrease (P < 0.001) and urgency disappearance. Slow incremental rectal filling drew a rectometrogram with a "tone" limb representing a gradual rectal pressure increase during rectal filling, and an "evacuation limb" representing a sharp pressure increase during balloon expulsion. The curve recorded both the 1st rectal sensation and the urgent sensation. CONCLUSION: The rectum has apparently two functions: transportation (conduit) and storage, both depending on the degree of rectal filling. If the fecal material received by the rectum is small, it is stored in the rectum until a big volume is reached that can affect a degree of rectal distension sufficient to initiate the defecation reflex. Large volume rectal distension evokes directly the rectoanal inhibitory reflex with a resulting defecation.

Study of the rectal electric activity of the uninhibited rectal detrusor (overactive rectum): a new concept of pathogenesis.

BACKGROUND/OBJECTIVE: One of the causes of fecal incontinence is uninhibited rectal detrusor syndrome (URDS). Patients with this condition either perceived the first rectal sensation after the onset of involuntary rectal contraction or not at all. We investigated the hypothesis that the abnormal rectal contractility in URDS may be caused by deranged rectal electric activity. METHODS: Twenty-five patients with URD (14 women and 11 men; age, 44.7 +/- 10.3 years) and 10 healthy volunteers (6 women and 4 men; age, 42.8 +/- 8.7 years) were studied. URDS was diagnosed by rectometry and provocative test. A transcutaneous EMG was performed with one electrode placed lateral to each sacroiliac joint and the third one midway between the greater trochanter and the ischial tuberosity. Two 20-minute recording sessions were performed for each subject. RESULTS: Slow waves (SWs) with regular rhythm and similar parameters (frequency, amplitude, conduction velocity) from the 3 electrodes were recorded from the healthy volunteers. They showed a significant increase in the parameters on saline filling of the rectum. The SWs of patients with URDS exhibited a "dysrhythmic" pattern with irregular parameters, which were different in the 3 electrodes and inconsistent during recording. They showed areas of tachyrhythmia, bradyrhythmia, and arrhythmia. On provoking rectal overactivity, the SWs showed an increased dysrhythmic activity. CONCLUSIONS: The patients with URD exhibited a "dysrhythmic" electric pattern with areas of variable electric activity. The tachyrhythmic areas seem to initiate the urgency and fecal incontinence of URDS. It is suggested that a disordered rectosigmoid pacemaker causes the dysrhythmic waves.

Measuring Students' Perceptions of Educational Environment in the PBL Program of Sharjah Medical College.

BACKGROUND: Students' perception of their educational environment has a significant impact on their behavior and academic progress. The recent worldwide usage of innovative problem-based learning (PBL) medical programs requires major changes in medical schools and their environments. Therefore, measuring students' perceptions of the complex PBL environment has become a critical necessity as a determinant of students' academic success and as a part of attaining the quality standards of education. Ours being a new medical college employing the PBL curriculum, it was important to measure the students' perception of the educational environment in order to identify the strengths and weaknesses of the curriculum and to plan for any future improvements. AIM AND OBJECTIVES: The aim of this study was to evaluate students' perceptions in the preclinical phase of the PBL educational environment in the College of Medicine, Sharjah Medical College, United Arab Emirates, and to recommend remedial procedures. MATERIAL AND METHODS: In this cross-sectional study, the English version of the Dundee Ready Education Environment Measure (DREEM) inventory was submitted to 250 students in years 1, 2, and 3. The data were analyzed using the SPSS 20 software, and significance was taken at P ≤ 0.05. The survey was performed in a mid-semester week, ie, in March 2014. No ethical issues were encountered during the process of this study. RESULTS: Two-hundred and fifty students responded to the questionnaire (100% response rate). The overall DREEM score was 113.4/200 (56.7%). First-year students expressed higher overall significant level of perception (119.4/200) than second-year (107.4/200) and third-year (112.7/200) students. In addition, first-year students perceived their learning, teaching, and academic climates as more significant than the other two batches. The scores obtained in the five domains were as follows; 28/48 in perception of learning, 26/44 in perception of teaching, 18/32 in academic self-perceptions, 27/48 in perceptions of atmosphere, and 15/28 in social self-perceptions. First-year students achieved the highest score (18.7/32) in the academic self-perception, and second-year students achieved the lowest (16.5/32). The total score was significantly higher in female students than in male students (115.9 vs 108.1). CONCLUSIONS: The present study revealed that the PBL environment is generally perceived positively by our medical students. Female students exhibited higher perception than male students. Nevertheless, areas such as curriculum overload and inadequate student support still require further fine-tuning and remedial measures.

Vesical pacing: pacing parameters required for normalization of vesical electric activity in patients with overactive bladder.

There are several modalities for the treatment of the overactive bladder (OAB), but the results may not be satisfactory. A recent study has demonstrated that the OAB has a dysrhythmic electric activity that seems to result from a disordered vesical pacemaker. We hypothesized that vesical pacing may correct the irregularities of the vesical electric waves and consequently normalize the vesical contractility. In this communication, we primarily defined the adequate pacing parameters required for correction of the vesical dysrhythmia. 36 patients with OAB were divided into a study group (22; 13 women; mean age 40.2 years) and a control group (14; 8 women; mean age 41.8 years). Ten healthy volunteers (6 women; mean age 39.8 years) were included in the study. Three 28-gauge cardiac pacing electrodes were hooked to the vesical mucosa: one (pacing) to the vault, and two (recording) to the lateral wall. Electric activity at rest and during stimulation of the pacing electrode was recorded in the study group and the healthy volunteers. In the control group, recording was done without pacing. Reproducible regular triphasic SWs were recorded from the 2 electrodes of the healthy volunteers with a similar pattern from the 2 electrodes of each individual subject. The optimal pacing parameters we determined were: an amplitude of 5 mA, a pulse width of 200 ms and a frequency of 20% higher than the frequency of the basal vesical waves. Vesical pacing effected a significant increase of waves' variables. The OAB patients exhibited a "dysrhythmic" wave pattern which was normalized during vesical pacing using the aforementioned pacing parameters. The optimal parameters required for vesical pacing of the dysrhythmic waves of the OAB were determined and succeeded in normalization of the vesical electric activity. Vesical pacing is suggested to be used as a therapeutic tool for the treatment of the OAB.

Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine.

1. Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea-pig small intestine in vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH- and S-type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S-type and increased in AH-type neurones. 2. The selective B(2) BK receptor antagonist HOE-140, but not the selective B(1) receptor antagonist des-arg(10)-HOE-140, suppressed the BK-evoked responses. RT-PCR confirmed the expression of B(2) receptor mRNA, but not B(1) receptor mRNA. 3. Binding of fluorescently- labeled HOE-140 (HOE741) was localized to ganglion cells in whole-mount preparations. BK B(2) receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase. 4. Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE-140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK. 5. The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E(2), D(2), F(2alpha) or I(2) mimicked the BK-evoked responses. 6. The results suggest that BK acts at B(2) BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.

Electric activity of the colon in subjects with constipation due to total colonic inertia: an electrophysiologic study.

BACKGROUND: Idiopathic constipation may result from colonic inertia, which affects the whole colon or is localized to an area of the colon. The colon exhibits electric activity in the form of slow waves or pacesetter potentials (PPs) and action potentials (APs), which are coupled with elevated colonic pressure. The APs are claimed to be responsible for colonic motor activity. HYPOTHESIS: Colonic electric activity is disordered in patients with constipation due to colonic inertia. METHODS: Electric activity was studied in 11 patients with colonic inertia and constipation (mean +/- SD age, 42.8 +/- 6.6 years; 7 women) who underwent total colectomy. Eight volunteers who had no gastrointestinal complaints (mean +/- SD age, 40.6 +/- 5.8 years; 5 women) acted as controls. Control subjects underwent laparotomy for hernia repair (n = 7 patients) and for removal of a mesenteric cyst (n = 1 patient). During the operation, 2 monopolar silver-silver chloride electrodes were applied to the cecum and the ascending, transverse, descending, and sigmoid colon. RESULTS: Electric waves (PPs and APs) were recorded from all parts of the colon in control subjects. The waves were monophasic, negatively deflected, and had regular rhythm. The wave variables from the 2 electrodes of each segment of the colon were identical and reproducible. They progressively increased aborally. In the colonic inertia group, 5 patients had recorded waves from the cecum and ascending colon but no waves from the rest of the colon. The wave variables were significantly lower than those of the controls (P =.02). In the remaining 6 patients, no waves were registered from the whole colon. CONCLUSIONS: Regular electric waves were recorded from the colons of control subjects. The aboral increase of their frequency, amplitude, and conduction velocity suggests that colonic motile activity increases analward, reaching its maximum in the sigmoid colon to expel its solid contents. We postulate that constipation in patients with colonic inertia is attributable to weak or absent electric activity, the cause of which is unknown. A disorder of the interstitial cells of Cajal, which generate electric activity, is suggested to have a role in inducing diminished or absent colonic motor activity, a point that should be investigated.

Effect of straining on diaphragmatic crura with identification of the straining-crural reflex. The "reflex theory" in gastroesophageal competence.

BACKGROUND: The role of the crural diaphragm during increased intra-abdominal pressure is not exactly known. We investigated the hypothesis that the crural diaphragm undergoes reflex phasic contraction on elevation of the intra-abdominal pressure with a resulting increase of the lower esophageal pressure and prevention of gastro-esophageal reflux. METHODS: The esophageal pressure and crural diaphragm electromyographic responses to straining were recorded in 16 subjects (10 men, 6 women, age 36.6 +/- 11.2 SD years) during abdominal hernia repair. The electromyogram of crural diaphragm was recorded by needle electrode inserted into the crural diaphragm, and the lower esophageal pressure by a saline-perfused catheter. The study was repeated after crural anesthetization and after crural infiltration with saline. RESULTS: The crural diaphragm exhibited resting electromyographic activity which showed a significant increase on sudden (coughing, p < 0.001) or slow sustained (p < 0.01) straining with a mean latency of 29.6 +/- 4.7 and 31.4 +/- 4.5 ms, respectively. Straining led to elevation of the lower esophageal pressure which was coupled with the increased electromyographic activity of the crural diaphragm. The crural response to straining did not occur during crural diaphragm anesthetization, while was not affected by saline infiltration. The lower esophageal pressure declined on crural diaphragm anesthetization. CONCLUSIONS: Straining effected an increase of the electromyographic activity of the crural diaphragm and of the lower esophageal pressure. This effect is suggested to be reflex in nature and to be mediated through the "straining-crural reflex". The crural diaphragm seems to play a role in the lower esophageal competence mechanism. Further studies are required to assess the clinical significance of the current results in gastro-esophageal reflux disease and hiatus hernia.

Effects of exposure to extremely low-frequency magnetic field of 2 G intensity on memory and corticosterone level in rats.

In the present study, we examined the effects of chronic exposure (1 and 2 weeks) to an extremely low-frequency magnetic field (ELFMF) of 2 G intensity on memory in rats using an object recognition task. Comparable groups of rats were exposed for 1, 2 or 4 weeks to ELFMF and the following day blood samples were collected from each rat for the measurement of corticosterone level. Our results demonstrate that exposure to ELFMF induces a significant increase in the level of corticosterone in blood plasma and is associated with impairment in discrimination between familiar and novel objects.

Effect of straining on the lower esophageal sphincter: identification of the "straining-esophageal reflex" and its role in gastroesophageal competence mechanism.

The lower esophagus is intra-abdominal and exposed to intra-abdominal pressure (IAP) variations that may lead to gastroesophageal reflux (GER). We investigated the hypothesis that the lower esophageal sphincter (LES) undergoes phasic contraction on IAP increase, with a resulting inhibition of the stress GER. The study comprised 17 subjects (age 42.3 +/- 8.7 SD yr, 10 men, 7 women) who were scheduled for surgical repair of abdominal hernia. The patients had no swallowing problems. The electromyographic (EMG) activity of the LES and pressure within the LES were recorded at rest and during increased IAP (coughing, straining). The recording was repeated after LES anesthetization or saline infiltration. The LES EMG at rest showed regular slow waves (SWs), superimposed on or followed by random action potentials (APs). Coughing or straining induced increase of the SWs parameters and also of the APs; although the increase with straining was less than with coughing, the difference was insignificant. Coughing or straining increased the LES pressure significantly (p < .05, p < .05, respectively). Ten minutes after LES anesthetization, coughing or straining did not produce significant LES EMG or pressure changes, while saline infiltration of LES caused LES response similar to preinjection. Thus, coughing and straining effected an increase of the LES EMG activity and pressure, an action presumably mediated through a reflex that we call the "straining-esophageal reflex." This reflex seems to be evoked during increased intra-abdominal pressure and to effect LES contraction, thus, sharing with other factors in prevention of gastroesophageal reflux.

Role of the rectosigmoid pacemaker and electric activity in rectal motility: mechanism and clinical significance.

BACKGROUND: The rectum exhibits electric activity in the form of slow waves or pacesetter potentials (PPs) and action potentials (APs), which are suggested to be initiated from a rectosigmoid pacemaker (RSP). We hypothesized that the RSP and electric waves are responsible for rectal motility. This hypothesis was investigated. METHODS: The rectum of 13 mongrel dogs was exposed through an abdominal incision, and 3 electrodes were fixed serially to the rectal serosa. The rectal pressure was measured by a 6 F saline-perfused catheter and the rectal electromechanical response to rectal balloon distension in increments of 5 ml of air was registered. The test was repeated after rectosigmoid junction (RSJ) anesthetization by 20 minutes and 3 hours using xylocaine injection. It was done also after saline instead of xylocaine injection. RESULTS: PPs and APs were recorded and had the same frequency, amplitude and conduction velocity from the 3 electrodes of the same animal. APs occurred randomly and were coupled with elevated rectal pressure. Rectal balloon distension produced increase of the rectal electric activity and pressure, which increased with the increase of the rectal distension until, at a mean volume of 31.2 +/- 5.4 ml, the balloon was expelled to the exterior. RSJ anesthetization abolished the rectal electric waves and effected no balloon expulsion with high volume rectal distension. The rectal waves appeared after waning of the anesthetic effect. Saline injection into the RSJ produced no significant effect on the rectal electromechanical activity. CONCLUSION: Rectal electric waves are suggested to be initiated from the RSP and to be responsible for the rectal motor activity. Incremental rectal balloon distension effected progressive increase of the rectal electromechanical activity until the balloon was expelled to the exterior RSJ anesthetization blocked the electric waves and the electromechanical response to rectal distension. These results have probably clinical significance when performing electrorectograms for various rectal pathologic conditions as well as when applying an artificial pacemaker to the non-contractile rectum.

Vesical pacing in patients with overactive bladder: technique and results.

OBJECTIVES: A recent study has demonstrated that the electric activity of the overactive bladder (OAB) is 'dysrhythmic'. The cause was attributed to a disordered vesical pacemaker which discharges these waves. In a subsequent study, the dysrhythmic waves have been 'normalized' by vesical pacing and the optimal parameters which are required to achieve normalization have been defined. We investigated the hypothesis that vesical pacing of the OAB might improve not only the vesical electric activity but also the symptoms. METHODS: Vesical pacing was used in 9 patients (age 39.2 +/- 10.3; 5 women, 4 men) with OAB. Under anesthesia, the pacemaker was implanted in an inguinal subcutaneous pocket and connected to 2 pacing electrodes implanted into the vesical vault. The normalization of the waves was tested by 2 recording electrodes which were temporarily applied to the vesical wall and removed post-testing. The pacemaker was then programmed for home pacing to be activated at given times. RESULTS: Vesical pacing effected normalization of the dysrhythmic electric waves with disappearance of the OAB symptoms in 7 patients and failed in 2. Vesical pacing was abandoned in 3/7 patients after a few months following the spontaneous disappearance of the symptoms. CONCLUSIONS: Vesical pacing has normalized the dysrhythmic electric activity and suppressed the symptoms of the OAB in 77.7% of patients. The pacemaker was removed in 5 patients: 2 failures and 3 after spontaneous waves normalization. No complications were encountered. Vesical pacing is suggested as a treatment for OAB when commonly used therapeutic modalities have failed.

Antioxidant effect of garlic (Allium sativum) and black seeds (Nigella sativa) in healthy postmenopausal women.

OBJECTIVES: The objective of this study is to investigate the antioxidant effects of garlic extract and crude black seeds' consumption on blood oxidant/antioxidant levels in healthy postmenopausal women. METHODS: In total, 30 healthy postmenopausal women (mean age = 50.31 ± 4.23 years) participated. They ingested two garlic soft gels per day (each is equivalent to 1000 mg of fresh garlic bulb) and crude black seed grounded to powder in a dose of 3 g/day for 8 weeks. Oxidant (malondialdehyde) activity in plasma and antioxidants superoxide dismutase and glutathione peroxidase activities in erythrocytes were studied. RESULTS: Significant low levels of plasma malondialdehyde with increased erythrocyte glutathione peroxidase and superoxide dismutase activities. DISCUSSION: Menopause is associated with an increase in oxidative stress and a decrease in some antioxidant parameters. Consumption of garlic extracts and crude black seeds may have a beneficial effect on improved balance between blood oxidants and antioxidants in healthy postmenopausal women.

Interstitial cells of Cajal, the Maestro in health and disease.

Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very significant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.