Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

Aquaporins in the Kidney: From Molecules to Medicine

https://www.imop.gr/sites/default/files/eau_guidelines_non-neurogenic_male_luts.pdf

EAU Guidelines on the Treatment and Follow-up of Non-neurogenic Male Lower Urinary Tract Symptoms Including Benign Prostatic Obstruction

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(08)00252-6.pdf

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets

To study the role of the urethra in bladder instability, we performed continuous urethrocystometry in 16 patients with verified unstable detrusor and found two qualitatively different pressure oscillations in the urethra: (1) continuous rhythmic pressure waves, characterized by frequency and pressure amplitude and (2) sudden and consistent urethral pressure drops of 35 cm H2O occurring on average at mean time intervals of 3.5 seconds prior to the onset of the detrusor contraction. Simultaneous pelvic floor electromyographic (EMG) registration showed that the urethral pressure drop occurred either during decreased, unchanged, or increased pelvic floor activity. Restoration of the urethral pressure to its previous level was also unrelated to the pelvic floor EMG activity. Increased EMG activity at the onset of urethral pressure drops was not sufficient to suppress the urethral pressure drop, but could abolish the detrusor contraction.



These findings suggest that the unstable detrusor is of a complex pathophysiological origin and involves both storage and micturition as well as detrusor and urethral function.

Continuous urethral pressure measurement in women with unstable detrusor

Can bladder fibrosis in congenital urinary tract obstruction be reversed

Percutaneous registration of renal pelvis pressure was undertaken successfully in 17 of 22 patients with unilateral hydronephrosis. Intrapelvic pressure was registered continuously during diuresis induced by mannitol and Urografin. In 10 cases additional increase in urine flow was induced by administration of furosemide. Ureteric urine flow was recorded through a cystoscopically introduced catheter on the side under investigation in 7 cases. The basic pressure was on average 12 mmHg and more than 20 mmHg in 2 cases only. No correlation was found between baseline pressure and degree of hydronephrosis. The intrapelvic pressure rose during forced diuresis with a few exceptions within normal limits. No correlation was demonstrated between pressure rise and renographically estimated kidney function. Pelvic peristaltic activity was detectable in only 3 cases. It is concluded that preoperative registration of renal pelvic pressure during diuresis as performed in this study is of no value in selection of the method of treatment in patients with hydronephrosis.

Percutaneous intrapelvic pressure registration in hydronephrosis during diuresis.

OBJECTIVE

To identify phenotypic characteristics in three large families with autosomal dominant nocturnal enuresis (NE), and to elucidate whether such characteristics persist after cessation of symptoms.



SUBJECTS AND METHODS

From three unrelated NE kindreds (A–C) we included 98 living members of whom 34 either had active NE (>one wet night/month after the age of 5 years) or a history of NE. The family members were interviewed to identify NE type and severity. Subsequently, night-time urine production was recorded for 2 weeks at home and 4 days of frequency-volume charts were completed.



RESULTS

There was coexistence of both primary and secondary NE (family A), coexistence of monosymptomatic NE and incontinence (families A and C), pure monosymptomatic NE (family B) and pure day-time incontinence (family C). However, the NE phenotype of family A was characterized by nocturnal polyuria and normal bladder capacity, whereas family C was characterized by normal nocturnal urine production and reduced bladder capacity. Interestingly, there were no differences between former affected and unaffected family members in any of the families for night-time urine production, nocturia frequency, nocturia volumes, day-to-night ratios, or bladder capacity.



CONCLUSION

The clinical phenotype in three large families with hereditary severe NE was heterogeneous within and between families. However, the NE phenotype seemed to differ between two of the families for nocturnal urine production, bladder capacity, and response to desmopressin. These results indicate that the genes responsible for NE in these families are not related directly to the presence of primary vs secondary NE or coexisting day-time problems. However, there might be genetically determined differences in bladder capacity and/or nocturnal urine production.

Hereditary phenotypes in nocturnal enuresis.

OBJECTIVE

To apply stereotactic electrical stimulation of the pig brainstem and thus identify a pontine micturition centre.



MATERIALS AND METHODS

In 10 anaesthetized female Vietnamese minipigs a needle-electrode was positioned in the pontine region. Pressure responses in the lower urinary tract identified the micturition centre functionally during electrical stimulation. Stereotactic coordinates were recorded, and the needle visualized by fluoroscopy, magnetic resonance imaging (MRI) or histologically.



RESULTS

The stimulation evoked responses similar to voiding, i.e. a urethral pressure decrease followed by a bladder pressure increase; or similar to a continence manoeuvre, i.e. urethral pressure increase and no change in bladder pressure. In a few cases a continence response was evoked by stimulating a site 1 mm away from the site where a voiding response was evoked. The electrode position was detected by the fluoroscopy-based stereotactic procedure followed by subsequent MRI (one animal), and by histological analysis, verifying it to be in the dorsolateral pontine region.



CONCLUSIONS

These results show that a pontine micturition centre exists in pigs similar to that described in rats, cats, dogs and humans.

Jens Christian Djurhuus

Papers

Continuous urethral pressure measurement in women with unstable detrusor

Can bladder fibrosis in congenital urinary tract obstruction be reversed

Percutaneous intrapelvic pressure registration in hydronephrosis during diuresis.

Hereditary phenotypes in nocturnal enuresis.

Stereotactic electrical stimulation of the pontine micturition centre in the pig.