The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural ...system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs.
► Suprasacral spinal cord injury (SCI) disrupts urine storage and voiding functions. ► SCI alters the morphology, chemistry and electrical properties of bladder afferent neurons ► Synaptic remodeling in the spinal micturition reflex pathway occurs after SCI. ► Nerve growth factor contributes to neuroplasticity of bladder and sphincter reflexes after SCI.
Background
Fermented milk products containing
Bifidobacterium breve
strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.
Aims
To assess efficacy of BFM in maintaining ...remission in Japanese patients with quiescent UC.
Methods
This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day
Bifidobacterium breve
strain Yakult (10 billion bacteria) and
Lactobacillus acidophilus
(1 billion bacteria) (
n
= 98) or matching placebo (
n
= 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC).
Results
An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (
n
= 195). Relapse-free survival was not significantly different between the BFM and placebo groups (
P
= 0.643; hazard ratio 1.16; 95% CI 0.63–2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in
Bifidobacterium
species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient).
Conclusions
BFM had no effect on time to relapse in UC patients compared with placebo.
Study Registration
UMIN000007593.
Introduction and hypothesis
We investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, ...on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant.
Methods
Chemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats. SSEA-3
+
Muse cells, SSEA-3
−
non-Muse cells or Hanks' balanced salt solution (HBSS; vehicle) were injected into the anterior and posterior bladder wall at each 1×10
4
cells/10 μl 6 h after HCl application. The sham group received HBSS without HCl instillation. Urinary frequency was assessed using metabolic cages, cystometrograms, nociceptive behavior, and histological analysis of the bladder and L6 spinal cord.
Results
Increases in urinary frequency and decreases in bladder capacity compared with the sham group were observed in the vehicle and non-Muse groups, but not in the Muse group, at 1 week. Significant increases in nociceptive behavior compared with the sham group and the expression of TNFα in the bladder and c-Fos in the bilateral dorsal horns of L6 spinal cord were also observed in the vehicle and non-Muse groups, whereas these changes were not seen in the Muse group at 1 week. Histological analysis exhibited a higher proportion of injected Muse cells remaining in the urothelial basal layer and lamina propria of the bladder than non-Muse cells until 4 weeks.
Conclusions
Muse cell therapy could be a promising modality for treating HIC.
Accumulating evidence indicates the importance of natural killer (NK) cells in controlling tumor growth and metastasis. NK cell subsets display diversities in their function and tissue distribution ...and Mac‐1hi CD27lo NK cells are the predominant population of lung‐resident NK cells. Although the lung is a major organ where primary tumor develops and cancer cells metastasize, there is no clear evidence whether circulating NK cells and/or tissue‐resident NK cells control tumor growth in the lung. In the present study, we examined an antitumor function of lung‐resident NK cells to control pulmonary tumor growth. In an orthotopic lung tumor model, NK cells controlled pulmonary tumor growth, and mature circulating NK cell subsets were increased in tumor‐bearing lungs through a C‐X‐C motif chemokine receptor 3 (CXCR3)‐dependent mechanism. Although such increase in migratory NK cell subsets can be blocked by anti‐CXCR3 treatment, there was no difference in pulmonary tumor growth in anti‐CXCR3‐treated mice compared with control mice. In addition to pulmonary tumor growth, lung‐resident NK cells, but not migratory NK cells, play a dominant role in controlling metastatic growth of cancer cells in lung. These results strongly indicate an importance of lung‐resident NK cells for controlling pulmonary tumor growth.
Although lung is a major organ where primary tumor develops and cancer cells metastasize, there is no clear evidence whether circulating NK cells and/or tissue‐resident NK cells control tumor growth in lung. Presented results indicate the importance of lung‐resident NK cells for controlling pulmonary tumor growth.
Background
Immunosuppressants lead to an increased risk of infection, but few prospective studies have assessed the incidence of opportunistic infections in inflammatory bowel disease (IBD) patients, ...a high proportion of whom are treated with immunosuppressants. The aim of this study was to assess the age distribution of Japanese IBD patients with opportunistic infections and the risk factors associated with these infections.
Methods
A multicenter, prospective study of 570 IBD patients was conducted. The patients were followed for up to 12 months to identify any new infections. The incidence of opportunistic infections and the age distribution of patients with these infections were analyzed. We carried out a case–control study in which 2 non-infected IBD patients were selected as controls for each case (infected IBD patient); the effect of medications on the infection rate was also examined.
Results
Fifty-two (9.1 %) of 570 IBD patients developed opportunistic infections. Herpes simplex virus and herpes zoster virus infections were observed in 29 and 16 patients, respectively. No cases of active tuberculosis were observed. The incidence of opportunistic infections in patients aged 50 years or over was significantly higher than that in the other age groups (
p
= 0.01). The use of steroids (
p
= 0.02), thiopurine (
p
< 0.01), and immunosuppressant combination therapy (
p
< 0.01) was associated with an increased rate of opportunistic infections. However, the use of infliximab was not associated with an increased rate of opportunistic infections (
p
= 0.62). Multivariate analysis indicated that the use of thiopurine was an independent risk factor for opportunistic infections (
p
< 0.01).
Conclusions
Age ≥50 years and the use of immunosuppressants are risk factors for opportunistic infections in patients with IBD. In our cohort, tuberculosis was not seen as a complication of immunosuppressant therapy.
Functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that ...coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. Neural control of micturition is organized as a hierarchic system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brainstem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brainstem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily during the early postnatal period, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults cause re-emergence of involuntary micturition, leading to urinary incontinence. The mechanisms underlying these pathologic changes are discussed.
Obsessive slowness, a symptom of obsessive-compulsive disorder (OCD), is characterized by compulsive behavior and significant slowness of movement. Primary obsessive slowness (POS) is defined as a ...condition in which a series of actions are segmented, and the patient spends an unlimited amount of time performing each action while checking each action, resulting in cessation or slowness of movement. It is often difficult to treat POS with exposure and response prevention, which is considered effective in general OCD, and no treatment has been established. Here, we discuss the effectiveness of psychoeducation and modeling using video recordings in the treatment of POS.
We report a case of POS in a 19-year-old woman. Each action was subdivided and ordered, and the patient could not proceed to the next action without confirming that the previous step had been performed. Therefore, she could not live her daily life independently; for instance, toileting and bathing required more than 1 h, even with assistance. After more than 5 months of long-term treatment, including pharmacotherapy, psychoeducation, and modeling with video recordings, she recovered to live her daily life independently.
Psychoeducation and behavioral therapy can effectively treat POS. Particularly, modeling with video recordings would be an easy-to-use option for POS treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI ...allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder-urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.
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