TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague- Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin- D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.
Animals ; Biological Transport ; Calcium/urine ; Calcium Channels/chemistry ; Calcium-Binding Protein, Vitamin D-Dependent/*biosynthesis ; Hydrochlorothiazide/pharmacology ; Hypercalciuria/*therapy ; Male ; Models, Biological ; Rats ; Rats, Sprague-Dawley ; Sodium/*metabolism ; Sodium-Hydrogen Antiporter/chemistry ; Sodium-Potassium-Chloride Symporters/metabolism ; TRPV Cation Channels/*biosynthesis/chemistry ; Thiazides/*pharmacology

BACKGROUND: Constipation occurs frequently in diabetes mellitus (DM). However, there are few reports that investigated the characteristics of constipation associated with DM. The purpose of this study was to evaluate the clinical features of constipation associated with DM. METHODS: Among constipated patients who visited Asan Medical Center from January 2000 to December 2004, 45 patients with DM (DM group) and 104 patients without DM (non-DM group) were included in this study. We reviewed the clinical presentation, results of anorectal manometry, colon transit time study, and defecogram. We also analyzed the response to biofeedback therapy. RESULTS: The severity of constipation symptoms before treatment was not different between DM and non-DM group. Patients with colon transit time over 56 hours were more frequent in DM group than in non-DM group (21/45, 46.7% vs. 31/104, 29.8% ; p=0.047). Among DM group, colon transit time and the duration of DM showed positive correlation (r=0.431, p=0.003). The resting anal sphincter pressure was significantly lower in DM group than in non-DM group (43.5+/-21.5 mmHg vs. 51.7+/-22.6 mmHg ; p=0.048). The results of defecography were similar between DM and non-DM group. Successful responses to biofeedback therapy were not different between DM and non-DM group (19/34, 55.9% vs. 43/79, 54.4% ; p=0.887). CONCLUSIONS: Slow transit constipation was more frequent in DM group than in non-DM group. The successful responses to biofeedback therapy appear to be similar between DM and non-DM group.
Anal Canal ; Biofeedback, Psychology ; Chungcheongnam-do ; Colon ; Constipation* ; Defecography ; Diabetes Mellitus* ; Humans ; Manometry ; Time and Motion Studies

A 75-year-old man with mild renal impairment was started on sunitinib for a metastatic gastrointestinal stromal tumor. After 7 months of this therapy, proteinuria became aggravated. Serum creatinine concentration was increased from 1.34 to 2.57 mg/dL 24 months after sunitinib administration. Hematologic features of thrombotic microangiopathy (TMA) were absent. Renal histology revealed endothelial swelling and plasmatic insudation of the glomeruli. Proteinuria and renal function improved after discontinuation of sunitinib. Our experience suggests that TMA associated with sunitinib can be diverse in onset and severity, and that the hematologic features of TMA may be absent.
Aged ; Creatinine ; Gastrointestinal Stromal Tumors ; Humans ; Indoles ; Proteinuria ; Pyrroles ; Thrombotic Microangiopathies ; Vascular Endothelial Growth Factor A

Solitary rectal ulcer syndrome is an uncommon, chronic benign condition characterized by rectal bleeding, the passage of mucus, tenesmus and excessive straining during defecation. Occasionally, solitary rectal ulcer syndrome has been reported to be associated with defecation disorder such as pelvic floor dyssynergia, rectal intussusception and rectal prolapse. However, it is ambiguous how these associated defecation disorders contribute to make the rectal ulcer. We report a case of solitary rectal ulcer syndrome suggesting the pathophysiology of rectal ulcer by typical findings of evacuation defecography and MR defecography. A 40-year-old man presented with lower abdominal pain, rectal bleeding, passage of mucus and tenesmus intermittently for the past 4 years. Colonoscopy showed a large geographic and circumferential ulcer at the 10 cm distance from the anal verge. A biopsy revealed fibromuscular proliferation of laminar propria, hyperplasia of crypt and focal superficial ulceration. Finally, he was diagnosed as solitary rectal ulcer syndrome. Evacuation defecography showed paradoxical movement of puborectal sling and unusual invagination of rectal walls during defecation. In addition, rectum showed spastic movement and anterior rectal wall directly merged into posterior rectal wall making a kissing appearance. The invagination of the rectum at evacuation defecography proved to be the rectal wall thickening at MR defecography. After 9 sessions of biofeedback therapy, his defecation symptoms improved. However, ulcer was still observed without interval change.
Abdominal Pain ; Adult ; Ataxia ; Biofeedback, Psychology ; Biopsy ; Colonoscopy ; Defecation ; Defecography* ; Hemorrhage ; Humans ; Hyperplasia ; Intussusception ; Mucus ; Muscle Spasticity ; Pelvic Floor ; Rectal Prolapse ; Rectum ; Ulcer*

BACKGROUND/AIMS: Among constipated patients, there is a subgroup of patients who complain about an absent or diminished sense of desire to defecate, suggesting that one of the causes of functional constipation may be impaired rectal sensation. Recently, electrical stimulation therapy (EST) has been used for the treatment of patients with urinary/fecal incontinence. The aim of this study was to evaluate the efficacy of EST for a subgroup of constipated patients with impaired rectal sensation. METHODS: Of the 130 patients with functional constipation as defined by Rome II criteria, 22 patients who had impaired rectal sensation (rectal desire threshold volume = 90 ml) were selected. Twelve patients were treated with EST and 10 patients with biofeedback therapy (BFT). RESULTS: The overall symptoms of the patients significantly improved after therapy in both groups (p<0.05). Interestingly, the sense of desire to defecate improved only after EST (p<0.05). Moreover, there was significant improvement in anal residual pressure after BFT solely (p<0.05). On the other hand, rectal sensory threshold volumes improved significantly after EST exclusively (p<0.05). CONCLUSIONS: This study has revealed that the efficacy of EST can be comparable to BFT in a subgroup of constipated patients, especially with impaired rectal sensation. EST could be considered an adjunctive therapeutic modality for the management of functional constipation with impaired rectal sensation.
Biofeedback, Psychology ; Constipation ; Electric Stimulation Therapy ; Electric Stimulation* ; Hand ; Humans ; Sensation* ; Sensory Thresholds

BACKGROUND/AIMS: Among constipated patients, there is a subgroup of patients who complain about an absent or diminished sense of desire to defecate, suggesting that one of the causes of functional constipation may be impaired rectal sensation. Recently, electrical stimulation therapy (EST) has been used for the treatment of patients with urinary/fecal incontinence. The aim of this study was to evaluate the efficacy of EST for a subgroup of constipated patients with impaired rectal sensation. METHODS: Of the 130 patients with functional constipation as defined by Rome II criteria, 22 patients who had impaired rectal sensation (rectal desire threshold volume = 90 ml) were selected. Twelve patients were treated with EST and 10 patients with biofeedback therapy (BFT). RESULTS: The overall symptoms of the patients significantly improved after therapy in both groups (p<0.05). Interestingly, the sense of desire to defecate improved only after EST (p<0.05). Moreover, there was significant improvement in anal residual pressure after BFT solely (p<0.05). On the other hand, rectal sensory threshold volumes improved significantly after EST exclusively (p<0.05). CONCLUSIONS: This study has revealed that the efficacy of EST can be comparable to BFT in a subgroup of constipated patients, especially with impaired rectal sensation. EST could be considered an adjunctive therapeutic modality for the management of functional constipation with impaired rectal sensation.
Biofeedback, Psychology ; Constipation ; Electric Stimulation Therapy ; Electric Stimulation* ; Hand ; Humans ; Sensation* ; Sensory Thresholds

PURPOSE: Hypercalciuria is a risk factor of renal calcium stone and proper initial management is dietary salt restriction. But the molecular mechanism responsible for this sodium calcium relationship remains unclear. The present study investigates the relationship between different amount of sodium intake and the expression level of transporters involved in the active calcium transport. METHODS: Sprague-Dawley rats were randomized into three groups: a normal salt group, a low salt group, and a high salt group. Expression of mRNA and protein of transient receptor potential vanilloid (TRPV) 5 and calbindin-D28K was determined by real-time quantitative PCR and western blots, respectively. RESULTS: Hematocrit and body weight showed no difference among the three groups. High salt diet led to significant increase in the amount of urinary calcium excretion and decreased mRNA expression of calbindin-D28K and TRPV5. Protein abundance of calbindin-D28K and TRPV5 was decreased but the result was statistically insignificant. Low salt diet decreased the amount of urinary calcium excretion without significant difference. Messenger RNA expression and protein abundance of calbindin-D28K and TRPV5 showed no difference, compared to those of normal salt group. CONCLUSION: These data suggest that high sodium intake increases urinary calcium excretion, which is accompanied by a decreased expression of calbindin-D28K mRNA.
Animals ; Blotting, Western ; Body Weight ; Calbindin 1 ; Calcium* ; Calcium-Binding Proteins ; Diet ; Hematocrit ; Hypercalciuria ; Kidney* ; Polymerase Chain Reaction ; Rats* ; Rats, Sprague-Dawley ; Risk Factors ; RNA, Messenger ; Sodium ; Sodium Chloride, Dietary ; Sodium, Dietary* ; TRPV Cation Channels

Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D3. Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
Animals ; Calcium/therapeutic use/urine ; Calcium Channels/genetics/metabolism ; Cholecalciferol/*toxicity ; Hydrochlorothiazide/*therapeutic use ; Hypercalciuria/chemically induced/*drug therapy ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride Symporter Inhibitors/*therapeutic use ; Sodium-Glucose Transporter 1/genetics/metabolism ; Sodium-Hydrogen Antiporter/genetics/metabolism ; Sodium-Potassium-Chloride Symporters/genetics/metabolism ; TRPV Cation Channels/genetics/metabolism