Contingent and non-contingent effects of heroin on mu-opioid receptor-containing ventral tegmental area GABA neurons

Opiate activation of mu-opioid receptors (muORs) in the ventral tegmental area (VTA) modulates gamma-aminobutyric acid (GABA) neurotransmission within the mesocorticolimbic dopamine (DA) reward system. We combined in vivo extracellular electrophysiological recordings in anesthetized and freely behaving rats with intracellular Neurobiotin filling and immunocytochemistry to characterize the effects of opiates on VTA GABA neurons, evaluate their discharge activity during opiate self-administration, and identify the cellular sites for opiate activation. We identified a subpopulation of VTA GABA neurons that was characterized by location, spike discharge profile, activation by microelectrophoretic DA, and response to internal capsule (IC) stimulation. Systemic administration of heroin or microelectrophoretic application of the selective muOR agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) reduced VTA GABA neuron firing rate (heroin IC(50) = 0.35 mg/kg) and was blocked by the muOR antagonist naloxone. Heroin also reduced IC-evoked post-stimulus spike discharges, a manifestation of gap-junction-mediated electrical coupling between VTA GABA neurons. The baseline firing rate of VTA GABA neurons significantly increased (239%) following the acquisition of heroin self-administration behavior and transiently increased during each response for heroin (105%), but decreased (49%) following heroin, similar to non-contingent heroin. Electrophysiologically characterized VTA GABA neurons were filled with Neurobiotin and labeled dendrites contained plasmalemmal muOR immunoreactivity. Dually labeled muOR dendrites contained dendrodendritic appositions characteristic of gap junctions. These findings indicate that inhibition of this population of GABAergic neurons by opiates acting on dendritic muORs has implications for modulation of electrical coupling between VTA GABA neurons and dopamine (DA) neurotransmission in the VTA and terminal field regions.     

Plasma serotonin in autism

Serotonin is necessary for normal fetal brain development. Administration of serotonin inhibitors to pregnant rats results in offspring with abnormal behaviors, brain morphology, and serotonin receptor numbers. Low maternal plasma serotonin may contribute to abnormal brain development in autism. In this study, plasma serotonin levels in autism mothers and control mothers of typically developing children were compared, and plasma serotonin levels in children with autism (n = 17) and their family members were measured. Plasma serotonin levels in autism mothers were significantly lower than in mothers of normal children (P = 0.002). Plasma serotonin levels correlated between autism mothers and their children, but differed between autistic children and their fathers (P = 0.028) and siblings (P = 0.063). Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.     

A critique of impedance measurements in cardiac tissue

The specific impedance of cardiac tissue cannot be measured directly. Instead, the investigator obtains voltage and current measurements and places them into a model of the tissue's structure to infer the impedances of elements of the model. If the model fails to describe major aspects of the real tissue, the results may be worthless, although possibly self-consistent. In the literature of impedance measurement in cardiac tissue, only rarely is the model explicitly described; more commonly, the tissue model is adopted implicitly when equations giving the impedance in terms of voltage and current measurements are adopted. This paper examines the series of models that have been used in specific impedance measurements of cardiac tissue and shows how the same or similar measurements can accurately describe tissue impedivity or can lead to significant errors when inadequate models such as isotropic and anisotropic monodomains (although a part of work of historical merit) are used.     

Mirabegron for Male Lower Urinary Tract Symptoms

Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with BPH often present with a combination of obstructive and overactive bladder (OAB) symptoms. It is postulated that bladder outlet obstruction (BOO) from BPH results in concomitant OAB symptoms through ischemic induced variations in the response to neurotransmitters of both the detrusor and the urothelium. This altered response leads to the pathologic activation of the micturition reflex, generating sensory dysfunction and involuntary bladder contractions. Alpha-1 adrenoceptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are commonly used to treat the BOO caused by BPH. Anticholinergic agents are frequently used to treat concurrently OAB symptoms caused by the BOO. Unfortunately, anticholinergic medications demonstrate bothersome side effects and a theoretical risk of urinary retention. Basic science and clinical research has led to the development of a new class of pharmaceuticals for the treatment of overactive bladder with diminished risk of urinary retention and lacking many anticholinergic side effects. This novel compound, mirabegron (Mybertriq, Astellas Pharma US, Inc.), is a β₃-adrenoceptor agonist and represents a promising new class of oral agents designed for the treatment of OAB symptoms, with minimal effect on voiding.     

恒河猴中TTV感染的回顾性实验研究

目的：了解接种患者血清的恒河猴能否复制ＴＴ病毒（ＴＴ ｖｉｒｕｓ,ＴＴＶ）,正常恒河猴中是否有ＴＴＶ感染,分析猴中ＴＴＶ基因结构特点。方法：用ＰＣＲ方法检测血清标本中ＴＴＶ ＤＮＡ,对ＴＴＶ ＤＮＡ阳性的标本进行序列测定。结果：健康猴中无ＴＴＶ感染;１０只接种患者血清的恒河猴中,经验检测有４只为ＴＴＶ阳性,将其中一株ＴＴＶ进行序列测定,该序列与日本ＴＴＶ部分基因相对应位置的核苷酸同源性为９６％,将     

Arthrofibrosis Associated With Total Knee Arthroplasty

Background

Arthrofibrosis is a debilitating postoperative complication of total knee arthroplasty (TKA). It is one of the leading causes of hospital readmission and a predominant reason for TKA failure. The prevalence of arthrofibrosis will increase as the annual incidence of TKA in the United States rises into the millions.

Outcome Following Debridement,Antibiotics, and Implant Retention in Hip Periprosthetic Joint Infection—An 18-Year Experience

Background

Debridement-antibiotics-and-implant-retention (DAIR) may be considered a suitable surgical option in periprosthetic joint infections (PJIs) with soundly fixed prostheses, despite chronicity. This study aims to define the long-term outcome following DAIR in hip PJI.

Vaginal vault prolapse in a patient with Mayer–Rokitansky–Küster–Hauser syndrome: a video case presentation

Introduction and hypothesis

Several reports have described vaginal prolapse in Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome patients after creation of a neovagina. To our knowledge, no reports of primary vaginal prolapse of a blind pouch without previous intervention, or surgery for this condition, have been described.

Methods

In this case report, we describe a 19-year-old woman with MRKH and complete prolapse of her shortened vaginal pouch. Surgical correction utilizing permanent suture-based sacrospinous ligament fixation was performed.

Results

The patient had a successful outcome.

Conclusions

Sacrospinous ligament fixation provided a safe and effective method for the management of vaginal pouch prolapse. Long-term follow-up is planned. To our knowledge, this is the first report describing surgical repair of primary prolapse of a blind vaginal pouch in the setting of MRKH.

     

Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

Background  

Some patients with gastroesophageal reflux disease (GERD) suffer from laryngopharyngeal reflux (LPR). There is no reliable diagnostic test for LPR as there is for GERD. We hypothesized that detection of pepsin (a molecule only made in the stomach) in laryngeal epithelium or sputum should provide evidence for reflux of gastric contents to the larynx, and be diagnostic of LPR. We tested this hypothesis in a prospective study in patients with LPR symptoms undergoing antireflux surgery (ARS).     

Statin use and decreased risk of benign prostatic enlargement and lower urinary tract symptoms

Study Type – Prevention (individual cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Statin medications reduce inflammation. Inflammation may be important in causing prostate enlargement and lower urinary tract symptoms in aging men. Therefore, statin use may decrease inflammation and help prevent prostate enlargement and lower urinary tract symptoms. Men who took statin medications were less likely to develop an enlarged prostate or lower urinary tract symptoms compared to men who did not take statins. Additionally, men who took statins for the longest period of time had the lowest risk of developing these urological problems. These results suggest that statin use may help prevent common urological problems in aging men.

OBJECTIVE

• ? To determine whether statin use is associated with a decreased risk of developing benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS).

SUBJECTS AND METHODS

• ? We conducted a retrospective, population‐based cohort study of 2447 men, 40–79 years of age, residing in Olmsted County, MN, USA, in 1990, and followed these men biennially through 2007.
• ? Cox proportional hazard models were used to assess associations between statin use and new onset of moderate/severe LUTS (American Urological Association Symptom Index score >7), a decreased maximum urinary flow rate (<12 mL/s) or BPE (prostate volume >30 mL).

RESULTS

• ? Statin use was inversely associated with new onset of LUTS (Hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.31–0.49), a decreased maximum flow rate (HR 0.53; 95% CI 0.34–0.82) and BPE (HR 0.40; 95% CI 0.23–0.69) after adjustment for baseline age and body mass index, diabetes, hypertension, coronary heart disease, smoking, alcohol use, activity level and non‐steroidal anti‐inflammatory use.
• ? The longest duration of statin use was associated with the lowest risk of developing each outcome (all tests for trend: P < 0.001).

CONCLUSION

• ? In this study, statin use was associated with a 6.5‐ to 7‐year delay in the new onset of moderate/severe LUTS or BPE.
• ? While men typically take statin medications to prevent coronary heart disease events and related outcomes, these data suggest that men who use statins may also receive urologic benefits.