What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

5HT expression in the stomach and duodenum of the Rhesus Monkey (Macaca mulatta).

This study aims to provide a histological description of different regions of the gastric and duodenal mucosa in Rhesus monkey, as well as to analyze the distribution and the relative frequency of 5-HT. The cardia region mucosa consists of simple columnar epithelium PAS + and AB + and the 5-HT cells were observed at the base of the gland (QA [5-HT cells]/mm²) = 8.72 ±â€¯4.98). The body region, has a smaller number of glands. The 5-HT cells were found predominant in the base of the gastric glands. QA= 6.96 ±â€¯3.81. When compared to body region, the stomach fundus has smaller gastric pits. The 5-HT cells are found at the base of the glands near the main cells. QA = 5.29 ±â€¯2.09. The pylorus region was found to have deep pits and well-developed gastric glands. The 5-HT cells are scarce, at the base of the pyloric gland. QA = 1.18 ±â€¯1.36. The duodenum presented goblet cells strong PAS + and AB +. 5-HT cells were found both in the lining epithelium and in the intestinal glands. QA = 8.16 ±â€¯2.59.

Efficacy of Modern Light Curing Units in Polymerizing Peripheral Zones in Simulated Large Bulk-fill Resin-composite Fillings.

The variation in micro-hardness (HV) within simulated large cavities (10 × 6 mm) filled in one increment with three bulk-fill resin-based composites (BF-RBC) was assessed by means of a universal hardness device. Modern blue and violet-blue light curing units (LCUs) were applied in three different positions, by rotating the LCU in 120° steps. The exposure distance was 3 mm. One center and two peripheral (4-mm apart from the center) HV line profiles were measured in 0.5-mm steps at 24 hours postpolymerization to calculate the depth of cure (DOC). Incident light, irradiance, and spectral distribution were recorded. A multivariate analysis (general linear model) assessed the effect of the varied parameters as well as their interaction terms on HV and DOC. The effect of LCU rotation was not significant ( p=0.109). The DOC varied between 3.46 mm and 5.50 mm and was more strongly influenced by the BF-RBC ( p<0.001, ηP2=0.774), followed by the width of specimen ( p<0.001, ηP2=0.554), while the influence of the LCU was very low ( p<0.06, ηP2=0.070). Whether a BF-RBC filling is cured as well in the periphery as in the center depends more on the material than on the curing unit used.

Modulation of the effects of lung immune response on bone marrow by oral antigen exposure.

Allergic airway inflammation is attenuated by oral tolerization (oral exposure to allergen, followed by conventional sensitization and challenge with homologous antigen), which decreases airway allergen challenge-induced eosinophilic infiltration of the lungs and bone marrow eosinophilia. We examined its effects on bone marrow eosinophil and neutrophil production. Mice of wild type (BP-2, BALB/c, and C57BL/6) and mutant strains (lacking iNOS or CD95L) were given ovalbumin (OVA) or water (vehicle) orally and subsequently sensitized and challenged with OVA (OVA/OVA/OVA and H2O/OVA/OVA groups, resp.). Anti-OVA IgG and IgE, bone marrow eosinophil and neutrophil numbers, and eosinophil and neutrophil production ex vivo were evaluated. T lymphocytes from OVA/OVA/OVA or control H2O/OVA/OVA donors were transferred into naïve syngeneic recipients, which were subsequently sensitized/challenged with OVA. Alternatively, T lymphocytes were cocultured with bone marrow eosinophil precursors from histocompatible sensitized/challenged mice. OVA/OVA/OVA mice of the BP-2 and BALB/c strains showed, relative to H2O/OVA/OVA controls, significantly decreased bone marrow eosinophil counts and ex vivo eosinopoiesis/neutropoiesis. Full effectiveness in vivo required sequential oral/subcutaneous/intranasal exposures to the same allergen. Transfer of splenic T lymphocytes from OVA/OVA/OVA donors to naive recipients prevented bone marrow eosinophilia and eosinopoiesis in response to recipient sensitization/challenge and supressed eosinopoiesis upon coculture with syngeneic bone marrow precursors from sensitized/challenged donors.

Enhanced parasympathetic activity of sportive women is paradoxically associated to enhanced resting energy expenditure.

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure.

Inhibition of long-term potentiation by CuZn superoxide dismutase injection in rat dentate gyrus: involvement of muscarinic M1 receptor.

Long-term potentiation (LTP) and long-term depression represent important processes that modulate synaptic transmission that carries out a key role in neural mechanisms of memory. Many studies give strong evidences on a role of the reactive oxygen species in the induction of LTP in CA1 region of hippocampal slices that was inhibited by adding the scavenger enzyme superoxide dismutase (SOD1). Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK-N-BE cells through microvesicles by an ATP-dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C-protein kinase C pathway activation. The aim of this study was to investigate the effect of intracerebral injection of SOD1 or the inactive form of enzyme (ApoSOD) on the modulation of synaptic transmission in dentate gyrus of the hippocampus in urethane anesthetized rats. The results of the present research showed that intracerebral injection of SOD1 and ApoSOD in the dentate gyrus of the rat hippocampal formation inhibits LTP induced by high-frequency stimulation of the perforant path. This result cannot be only explained by the dismutation of oxygen radical induced by SOD1 since also ApoSOD, that lacks the enzymatic activity, carries out the same inhibitory effect on LTP induction.

Differential accumulation levels in the brain of rats exposed to the endocrine disruptor 4-tert-octylphenol (OP).

Octylphenol (OP) is an endocrine-disrupting chemical that accumulates in various organs. It has also been shown to exert noxious effects on the central nervous system. In the present study, we measured in Sprague-Dawley rats the degree of OP accumulation in different areas of the brain and investigated the effect of OP in pain modulation. Two groups of male Sprague-Dawley rats were treated for 20 days with 50mg/kg BW/day of OP (group 1) or vehicle (group 2). At the end of the treatment, the formalin test was performed to evaluate the effect of OP exposure on pain. Soon after, rats were sacrificed, and the accumulation of OP in the cerebral cortex, hippocampus, hypothalamus, cerebellum, thalamus, striatum, mesencephalus and ventral hindbrain was measured by HPLC analysis. The results showed a greater accumulation of OP in the cerebral cortex compared to all the other areas; there was also more accumulation in the cerebellum compared to the mesencephalus and thalamus. No accumulation was found in the striatum. These results suggest that there is a preferential accumulation of OP in different areas of the brain with consequences to neural behaviour. On the contrary, experiments on facial grooming did not show significant effects of OP on pain.

Proficient manipulation of fibreoptic bronchoscope to carina by novices on first clinical attempt after specialized bench practice.

BACKGROUND: Proficient manipulation of the fibreoptic bronchoscope is an important component of competent bronchoscopic airway management. We studied the duration of specialized bench training necessary to achieve this proficiency and the subsequent transfer of this psychomotor skill to human subjects. METHODS: Twenty-nine novice endoscopists undertook the training associated with a commercial non-anatomic endoscopic dexterity training system, Dexter. Bronchoscopic driving performance was assessed after each hour of self-directed training, using a global rating scale from 1 (unskilled) to 5 (expert) with a score of 3 linked to proficiency. The scale was applied to anonymized recordings of the endoscopic view as the bronchoscope was manipulated from the mouth to the carina of an anatomic manikin. Once bench proficiency was achieved, the ability of participants to perform the skill on volunteer co-participants was assessed. RESULTS: Ninety-six per cent of participants achieved proficiency on the manikin within 4 h of practice. Ninety-three per cent then drove the bronchoscope proficiently from the mouth to the carina of clinical volunteers on the first attempt. CONCLUSIONS: The endoscopic dexterity required to proficiently drive a bronchoscope in human subjects to an anatomic endpoint relevant to fibreoptic intubation is achievable after 2-4 h of specialized bench training. Training in the local environment may be more conducive to success than in time-limited workshops. Achieving a defined proficiency standard on bench models contributes to the development of basic bronchoscopic competence. This has the potential to protect patients from novice learning curves, optimize clinical education and efficiency, and assist compliance with difficult airway algorithms.

Mastication overload causes an increase in O2- production into the subnucleus oralis of the spinal trigeminal nucleus.

The aim of the present study was to evaluate the production of superoxide anion (O(2)(-)) in the trigeminal complex nuclei after a functional mechanical overload of the teeth due to the preference for masticating on one side in rats. The preference for masticating on one side was induced by the discomfort due to a small abrasion of one molar; such lateralisation in mastication was confirmed by electromyography. The production of O(2)(-) was evaluated in the trigeminal nuclei by fluorescence microscopy after an injection of dihydroethidium. The results showed that there was an increased production of O(2)(-) in the subnucleus oralis of the spinal trigeminal nucleus in the same side where the mastication was preferred. This result demonstrates that an increased activity of non-painful sensory neurons can enhance the production of reactive oxygen species within the central second order sensory nuclei.

Inhibition of prostaglandin synthesis reduces the induction of MyoD expression in rat soleus muscle.

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration.

Espresso coffee increases parasympathetic activity in young, healthy people.

Caffeine induces modifications of activity of the autonomic nervous system. This study analyzed the effect of a cup of espresso coffee on the heart rate variability (HRV) power spectral analysis, which is a method providing evaluation of the sympathetic and parasympathetic discharge. In young, healthy sedentary subjects (10 male, 10 female; aged 25-30 years), the HRV-power spectrum was evaluated over a period of 150 min after the administration of espresso coffee (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and seated position. Absolute values of the spectrum were summed in low (LF) and high frequencies (HF). The LF and HF spectra were used to estimate the sympathetic and parasympathetic activity, respectively. In the supine position, coffee increases HF, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by coffee or decaffeinated coffee. Coffee and decaffeinated coffee do not induce any modification of LF in both positions. This experiment indicates that espresso coffee influences parasympathetic activity in the supine position.

The synthesis of azadirachtin: a potent insect antifeedant.

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.

Resting energy expenditure and fat-free mass do not decline during aging in severely obese women.

BACKGROUND & AIMS: Few studies have investigated the age-related modification of resting energy expenditure (REE) and free fat mass (FFM) in severe obesity. This cross-sectional study analyzed REE and FFM in severely and moderately obese women and in lean subjects at different ages to find the possible differences between obese and lean subjects during aging. METHODS: Sedentary women (n=261) were divided into three groups with different body mass indexes (BMIs): 20.0-24.9; 30-34.9; >40 kg/m(2). Each group was then divided into five subgroups: 20-29; 30-39; 40-49; 50-59; 60-69 years. REE was measured with an indirect calorimetric device. The FFM was calculated by bioelectric impedance. RESULTS: The REE in severely obese women was higher than the REE in lean or moderately obese women. The FFM of severely obese women was lower than that of moderately obese or lean women. The aging induced reductions of the REE and FFM in lean and moderately obese subjects, but not in women with severe obesity. CONCLUSIONS: This experiment indicates that REE and FFM do not decline during aging in women with BMI>40, suggesting that the severe obesity induces different age-related adaptations of metabolism and body composition.

Cortical spreading depression induces the expression of iNOS, HIF-1alpha, and LDH-A.

The mechanisms of tolerance to subsequent episodes of ischemia induced by cortical spreading depression (CSD) are not clear. The effects of CSD on the expression of inducible nitric oxide synthase (iNOS), hypoxia inducible factor-1alpha (HIF-1alpha), and lactate dehydrogenase-A (LDH-A) were evaluated in the present experiment. Unilateral CSD was induced in Sprague-Dawley rats by application of KCl on the right cortex and the mRNA levels of iNOS, HIF-1alpha, and LDH-A were evaluated at 15 min, 2 h, 4 h, 6 h or 24 h after CSD. RT-PCR analysis showed: 1) an increase of iNOS mRNA at 15 min, 2 h, 4 h; 2) an increase of HIF-1alpha mRNA at 6 h; 3) an increase of LDH-A mRNA at 4 h. In situ hybridization with specific digoxigenin-labeled oligonucleotides revealed that the mRNA levels were increased at 15 min-2 h for iNOS, 2-4 h for LDH-A and 6 h for HIF-1 after CSD. Immunohistochemistry analysis revealed that levels of iNOS and HIF-1alpha were increased, respectively, at 2 h and 6 h after CSD. These data suggest that CSD promotes the expression of iNOS, HIF-1alpha, and LDH-A in nervous cells giving a neuroprotective effect.

Intracerebroventricular injection of oxidant and antioxidant molecules affects long-term potentiation in urethane anaesthetized rats.

Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebro-ventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-L-cysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthine-oxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H(2)O(2) injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection.

Activity of autonomic nervous system is related to body weight in pre-menopausal, but not in post-menopausal women.

This study analyzed vegetative modulation, expressed as heart rate variability (HRV) power spectral analysis, in lean and obese women at pre-menopausal or post-menopausal age to reveal possible differences in menopause-related autonomic activity in lean and obese subjects. Sedentary women (n = 40) were divided in four groups: pre-menopausal lean and obese women, post-menopausal lean and obese subjects. The HRV-power spectrum was evaluated on a 5-min long ECG recording. The absolute values of the spectrum were summed in the following frequencies: a low-frequency (0.04-0.15 Hz; LF) and high-frequency (0.15-0.40; HF) range. LF and HF were values used to estimate the sympathetic and parasympathetic activity. LF and HF values of pre-menopausal obese women are lower than values of lean women. The menopause induced a same decrease in LF and HF values in lean and obese subjects, so that no difference was found in post-menopausal groups. This experiment indicates that modifications of autonomic modulation can be included among factors related to obesity in pre-menopausal, but not post-menopausal women.

Immunohistochemical distribution of proteins belonging to the receptor-mediated and the mitochondrial apoptotic pathways in human placenta during gestation.

The balance between cell death and cell proliferation and its regulation are essential features of many physiological processes and are particularly important in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell suicide that is activated in two main ways: through a receptor-mediated pathway or through a mitochondrial pathway. We have investigated the immunohistochemical distribution of proteins belonging to these two pathways in human placenta during gestation by comparing their expression levels between the first and third trimester of gestation. In the first trimester, the receptor-mediated pathway prevails over the mitochondrial pathway with a moderate/intense expression of its three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak positivity of anti-apoptotic FLIP, these proteins being mainly localized in the cytotrophoblast compartment. In the third trimester of gestation, there is an increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase-9. We have also investigated the expression level of caspase-3, the primary effector caspase of both pathways, and have observed that it is moderately expressed during gestation, being mainly localized in the cytotrophoblast during the first trimester and in both placental compartments during the third trimester of gestation. Thus, both pathways actively function in human placenta to execute cell death. By means of immunoelectron microscopy, we have further shown that, in human placenta, the two proteins of the mitochondrial pathway together with caspase-3 are localized both in the cytoplasm and in the nucleus. In particular, Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an important role for these two proteins in disrupting the nuclear-cytoplasmic barrier.

Detachable snare versus epinephrine injection in the prevention of postpolypectomy bleeding: a randomized and controlled study.

BACKGROUND AND STUDY AIMS: Several endoscopic techniques have been developed to prevent bleeding after the removal of large pedunculated polyps. PATIENTS AND METHODS: From January 1995 to December 2002, 488 consecutive patients with pedunculated colorectal polyps, the heads of which were larger than 10 mm in diameter, were randomly assigned to three groups. In group A (163 patients), detachable snares were placed at the base of the stalk and standard snares were then used for polypectomy. In group B (161 patients), the polyp stalk was injected with a 0.01 % epinephrine solution before conventional snare polypectomy. Group C (a control group including 164 patients) underwent conventional snare polypectomy without preventive measures. Early (< 24 h) and late (> 24 h - 30 days) bleeding complications were assessed. Each group was divided into two subgroups relative to the polyp size (polyps 1.0 - 1.9 cm and polyps > or = 2 cm). RESULTS: Overall bleeding complications occurred after 4.3 % of the polypectomies. Bleeding was successfully controlled in all patients, and no blood transfusions were required. There were three cases of bleeding in group A (1.8 %), five in group B (3.1 %), and 13 in group C (7.9 %). Early bleeding was more frequent than late bleeding (15 vs. six patients). In polyps > or = 2 cm (207 patients), postpolypectomy bleeding occurred in 14 patients (6.7 %): two (2.7 %) in the detachable snare group, two (2.9 %) in the epinephrine injection group, and 10 (15.1 %) in the control group. CONCLUSIONS: These results show that polypectomy of large pedunculated polyps is associated with a higher incidence of bleeding. Particularly in polyps larger than 2 cm, preventive measures can significantly reduce bleeding complications after polypectomy. This can be achieved with similar efficacy either by placing Endoloops or by injecting epinephrine.

Extracellular GABA in the medial hypothalamus is increased following hypocretin-1 administration.

AIM: Hypocretin 1 is an hypothalamic neuropeptide that induces an increase in food intake when administered into the cerebral lateral ventricle. As it is well known that the medial hypothalamus (MH) is involved in the feeding behaviour also through GABAergic circuits, the aim of this experiment was to investigate the effect of an hypocretin 1 intracerebroventricular (icv) injection on the extracellular levels of GABA in the MH. METHODS: GABA levels in the MH were evaluated in six rats by microdialysis and high performance liquid chromatography-electrochemical detection 30 min before and every 30 min for an over all period of 6 h after an icv injection of hypocretin 1. The same procedure was used in another group of six rats but saline was injected into the lateral ventricle as control. RESULTS: The results show that extracellular GABA increases in the MH after the injection of hypocretin 1 at 60 min and at 3 h after the injection. CONCLUSION: This finding suggests a possible mechanism by which hypocretin 1 should induce hyperphagia in the first hour after injection. As it is already known that the inhibition of the MH by injection of GABA causes an increase of food intake, it is possible that hypocretin 1 causes an increase in food intake by increasing the GABA release in the MH. The lack of an increase in the GABA level after the fourth hour is consistent with the lack of an increase in food intake at this time, as we observed in previous experiments. The finding of a biphasic increase in the GABA level, at 60 min and at 3 h, was unexpected and should be further investigated.