The antioxidant l-Ergothioneine prevents cystine lithiasis in the Slc7a9-/- mouse model of cystinuria.

The high recurrence rate of cystine lithiasis observed in cystinuria patients highlights the need for new therapeutic options to address this chronic disease. There is growing evidence of an antioxidant defect in cystinuria, which has led to test antioxidant molecules as new therapeutic approaches. In this study, the antioxidant l-Ergothioneine was evaluated, at two different doses, as a preventive and long-term treatment for cystinuria in the Slc7a9-/- mouse model. l-Ergothioneine treatments decreased the rate of stone formation by more than 60% and delayed its onset in those mice that still developed calculi. Although there were no differences in metabolic parameters or urinary cystine concentration between control and treated mice, cystine solubility was increased by 50% in the urines of treated mice. We also demonstrate that l-Ergothioneine needs to be internalized by its transporter OCTN1 (Slc22a4) to be effective, as when administrated to the double mutant Slc7a9-/-Slc22a4-/- mouse model, no effect on the lithiasis phenotype was observed. In kidneys, we detected a decrease in GSH levels and an impairment of maximal mitochondrial respiratory capacity in cystinuric mice that l-Ergothioneine treatment was able to restore. Thus, l-Ergothioneine administration prevented cystine lithiasis in the Slc7a9-/- mouse model by increasing urinary cystine solubility and recovered renal GSH metabolism and mitochondrial function. These results support the need for clinical trials to test l-Ergothioneine as a new treatment for cystinuria.

Biliary antibiotics irrigation for E. coli-induced chronic proliferative cholangitis and hepatolithiasis: A pathophysiological study in rabbits.

BACKGROUND: The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis. METHODS: Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, Collagen-I, ß-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues. RESULTS: The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, ß-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05). CONCLUSIONS: LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.

Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.

Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.

Effects of polyphenols from grape seeds on renal lithiasis.

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Seventeenth-century 'treasure' found in Royal Society archives: the Ludus helmontii and the stone disease.

Our archival researches at the Royal Society reveal that a small envelope attached to a 1675 letter from an Antwerp apothecary, A. Boutens, contained a sample of the 'Ludus' prepared as a remedy for the 'stone disease' then sweeping through Europe, which was first announced in J. B. van Helmont's De lithiasi (1644). After examining the fascination with the medical use of the Ludus (which required the 'alkahest' for its preparation) and the tenacious efforts to procure it, we trace the fortunae of two other ludi in England, brought to and offered by Francis Mercurius van Helmont during his English sojourn. Both eventually found their way to the geologist John Woodward, one of them through Sir Isaac Newton. Finally we show how the allure of the Ludus helmontii vanished, with transformations in mineral analysis and reclassifications from Woodward to John Hill.

Diuretic and antilithiasic activities of ethanolic extract from Piper amalago (Piperaceae).

OBJECTIVE: Piper amalago is used in Brazilian folk medicine as diuretic and for the treatment of urinary calculus disease, although no scientific data have been described to support these effects. Thus, this study aims to evaluate the diuretic effects and antilithiatic activity of the ethanolic extract of P. amalago (EEPam). MATERIALS AND METHODS: Ethanolic extracts of P. amalago (125, 250 and 500mg/kg) were orally administered in male Wistar rats (n=5) and urinary excretion was measured at intervals of up to 24h after administration. The antilithiasic effect of EEPam on calcium oxalate urolithiasis crystallization was examined in a turbidimetric model. RESULTS: The oral administration of all doses of EEPam significantly increased urine output after 24h when compared to control group. Moreover, the application of EEPam, induced an inhibitory effect on calcium oxalate crystallization. CONCLUSIONS: According to results, P. amalago extracts showed diuretic and natriuretic activity and antilithiasic effects.

Avaliação da influência da orientação nutricional e do tratamento medicamentoso na recorrência da litíase urinária / Evaluation of the influence of nutritional guidance and drug therapy recurrence of urolithiasis

A litíase urinária é a terceira causa mais comum de afeção do trato urinário. A orientação dietética e o tratamento medicamentoso específico são importantes na recorrência da litíase e, portanto, mudar a dieta e seguir o tratamento farmacológico específico pode prevenir a sua recorrência. Avaliar a influência da orientação nutricional e do tratamento medicamentoso na recorrência da litíase urinária. A partir do nosso registro de pacientes com litíase recorrente foram selecionados 57 que tiveram pelo menos 5 anos de seguimento. Intervenção: Durante o acompanhamento dos pacientes foram avaliados os seguintes parâmetros: questionário clínico, investigação metabólica e avaliação por imagem (ultra-sonografia e/ou raio-X simples de abdome). Todos os pacientes foram orientados a controlar a ingestão de proteína (entre 0,8 a 1g/Kg peso corporal/dia) e adequar a ingestão de cálcio (entre 800 a 1000 mg/dia), levando-se em consideração o registro alimentar de 3 dias. A restrição de sal (menor que 5 g/dia) foi realizada tendo como referência a variação do sódio excretado na urina de 24h. Durante o acompanhamento os pacientes receberam ainda orientações dietéticas e farmacológicas específicas de acordo com o distúrbio metabólico identificado. 56% dos pacientes eram sexo masculino e a média do IMC no pré-tratamento foi de 27,8 kg/m², observando-se uma correlação positiva entre o número médio de cálculos formados por ano no pré-tratamento e IMC (p=0,012) Notamos uma diminuição significativa do cálcio, sódio e ácido úrico na urina de 24 horas no pós tratamento em comparação ao período inicial. Observamos um aumento significativo do citrato na urina de 24 horas no pós-tratamento. O nº de cálculos formados durante seguimento de 5 anos, diminuiu significativamente em relação ao pré tratamento...

Urinary tract lithiasis is the third most common cause of urinary tract affection. Dietary factors have great importance in the formation of urolithiasis; therefore, changing the diet and specific pharmacological treatment can prevent its recurrence. Evaluate the influence of clinical therapy associated to nutritional orientation in the recurrence of urolithiasis. From our registry of patients with recurrent lithiasis we selected 57 who had at least 5-years of follow-up. We used the protocol composed by 2 non-consecutive urine samples of 24h and was performed: Ca, Na, uric acid, citrate, oxalate, Mg and urinary volume assessments. In the pre treatment the lithiasis clinical questionary and after five years was care out using abdomen x-ray and/or ultrasound. Individualized dietary orientation consisted of: to increase fluid intake (enough to form ≥ 2 L / day); sodium ingestion <5 g / day and protein intake range between 0.8 - 1 g / kg body weight / day, and the adequate calcium intake (800 to 1000 mg / day). During the follow-up of patients, specific and individualized dietary orientation was performed according to the diagnosed metabolic disorder. Patients received specific pharmacological treatment according to the metabolic alteration. 54% were male. In average the BMI was 27 kg / m2. It was observed that according to BMI classification, the patients were overweight. Urinary excretion of calcium, uric acid and sodium decreased significantly after 5 years of follow-up. The number of stones formed in the 5- year follow-up decreased significantly compare to pre treatment. Individualized dietary orientation and pharmacological...

Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis?

AIM: To evaluate the long-term results of liver resection for the treatment of primary intrahepatic lithiasis. Prognostic factors, especially the impact of bilioenteric anastomosis on recurrence of symptoms were assessed. METHODS: Forty one patients with intrahepatic stones and parenchyma fibrosis/atrophy and/or biliary stenosis were submitted to liver resection. Resection was associated with a Roux-en-Y hepaticojejunostomy in all patients with bilateral stones and in those with unilateral disease and dilation of the extrahepatic biliary duct (> 2 cm). Late results and risk factors for recurrence of symptoms or stones were evaluated. RESULTS: There was no operative mortality. After a mean follow-up of 50.3 mo, good late results were observed in 82.9% of patients; all patients submitted to liver resection alone and 58.8% of those submitted to liver resection and hepaticojejunostomy were free of symptoms (P = 0.0006). Patients with unilateral and bilateral disease showed good late results in 94.1% and 28.6%, respectively (P < 0.001). CONCLUSION: Recurrence of symptoms in patients with hepaticojejunostomy showed that this may not be the ideal solution. Further studies are needed to establish the best treatment for patients with bilateral stones or unilateral disease and a dilated extrahepatic duct.

Comparatively lower postoperative hepatolithiasis risk with hepaticocholedochostomy versus hepaticojejunostomy.

BACKGROUND: Optimal surgical technique plays a key role in preventing the postoperative recurrence of hepatolithiasis. Tian et al developed the subcutaneous tunnel and hepatocholangioplasty using the gallbladder (STHG) technique and applied it in hepatolithiasis patients who had an approximately normal gallbladder and sphincter of Oddi. However, the technique is controversial. In the present study, a canine model was established for hepatocholangioplasty (HC) and hepaticojejunostomy (HJ) to simulate STHG and Roux-en-Y cholangiojejunostomy in the clinic, respectively. Then, the alterations of bile components in the vicinity of the anastomosis were compared. This may provide an experimental guide for choosing an optimal technique for the treatment of hepatolithiasis in the clinic. METHODS: The animals were randomly separated into a control group (5 dogs) and a model group (stenosis of the common bile duct; 24 dogs). The 24 dogs in the model group were randomly divided into an HC group and an HJ group (12/group). Bile was collected from the bile duct at 1 and 5 months after the operation, and the bile components were determined. RESULTS: The levels of total bile acid, cholesterol, total bilirubin, and phospholipid in the HC group were higher than those in the HJ group (P<0.05). However, no statistical difference was seen in unconjugated bilirubin and calcium ions. The mucin level in bile in the HC group was lower than that in the HJ group at 5 months after the operation (P<0.05). The postoperative lipid peroxidation level was remarkably lower than that in the HJ group (P<0.05). However, the superoxide dismutase level was remarkably higher than that in the HJ group (P<0.05). Finally, a significant difference was found in the positive bacterial culture rate in bile between the groups. CONCLUSION: Changes of bile components near the anastomosis after HC might be more preferable for preventing hepatolithiasis formation than HJ.

Sphincter of Oddi laxity: an important factor in hepatolithiasis.

AIM: To evaluate the importance of sphincter of Oddi laxity (SOL) in hepatolithiasis (HL). METHODS: Subjects included 98 patients diagnosed with HL between 2002 and 2007. Detailed histories were taken and the subjects were monitored until July 2008. HL patients were divided into two groups: Group I included 45 patients with SOL, and Group II included 53 patients without. Recurrence and reoperation indices of both groups were calculated and compared. RESULTS: The recurrence index was 0.135 in Group I and 0.018 in Group II (P < 0.001). The reoperation index was 0.070 in Group I and 0.010 in Group II (P < 0.001). The mean frequency of biliary operation was 2.07 in Group I and 1.21 in Group II (P = 0.001). Differences between the two groups are significant. CONCLUSION: HL patients with SOL tend to have a higher risk of recurrence and a larger demand for reoperation than those without this condition.

Influence of diet and water supply on mineral content and pH within the large intestine of horses with enterolithiasis.

To determine the effects of two diets and water supplies on intestinal pH and mineral concentrations in the colon of horses, and to identify whether differences in these parameters exist in horses with and without enterolithiasis, surgical fistulation of the right dorsal colon was performed in six adult horses, three with and three without enterolithiasis. Each horse underwent four feeding trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered/softened water, and alfalfa hay with filtered/softened water. Samples of colonic contents were analyzed for pH, dry matter, and mineral concentrations. Horses with enterolithiasis had higher calcium, magnesium, phosphorus and sulfur concentrations and higher pH in colonic contents than controls. Horses fed alfalfa had lower colonic sodium and potassium, higher calcium, magnesium, phosphorus and sulfur concentrations, and a more alkaline pH than those fed grass. Grass hay consumption leads to reduced concentrations of select minerals and a more acidic colonic environment compared with alfalfa, probably beneficial in the prevention of enterolithiasis. Under controlled dietary and management conditions, horses with enterolithiasis have differences in colonic mineral and pH parameters that may be consistent with physiological differences between horses with and without the disease.

Evaluation of dietary and management risk factors for enterolithiasis among horses in California.

Enteroliths are intestinal calculi that result in intestinal obstruction and colic in horses. Equine enterolithiasis occurs worldwide, but the disease is particularly prevalent in some geographic locations, including California. The objectives of this study were to evaluate dietary and environmental risk factors for the disease. This was accomplished through a case-control study by comparing horses with colic from enterolithiasis presenting to the University of California, Davis VMTH, to horses with colic of other causes. Data were collected on 61 horses with enterolithiasis and 75 controls via evaluation of patient records and questionnaires completed by owners at the time of admission. Following multiple logistic regression analysis, the following factors were found to be significantly associated with enterolithiasis: feeding > or = 50% of the diet as alfalfa; feeding <50% of the diet as oat hay; feeding <50% of the diet as grass hay; and lack of daily access to pasture grazing.

Tratamiento de la Litiasis Biliar por mini-incisiones adaptadasy por videolaparoscopia: Estudio prospectivo y comparativo / Treatment of the Litiasis Biliar for mini-incisions adaptadasy for videolaparoscopia: Market and comparative study

Antecedentes: La colecistectomía ha sido unánimemente considerada como el método ideal para el tratamiento de la colélitiasis por más de 100 años. Desde la década pasada, se considera a la colecistectomía por video-laparoscópica como el gold-standard. Objetivos: El objetivo de este estudio es evaluar los resultados obtenidos con la mini- incisiones adaptadas y con la video-laparoscopia en el tratamiento de la colecistolitiasis, ampliando en esta experiencia el mismo concepto, pero aplicándolo al tratamiento de la litiasis de la vía biliar principal. Diseño: Prospectivo y comparativo protocolizado.Lugar de aplicación: Servicio de Cirugía General “Pablo Luis Mirizzi” del Hospital Nacional de Clínicas y en nuestra practica profesional privada Clínica Caraffa. Material y Metodos: En el presente trabajo se analiza dos grupos de pacientes en el tratamiento de la litiasis biliar electiva y sus complicaciones entre enero de 2000 y diciembre del 2006. En el primero (Grupo 1), se operaron 370 pacientes que se realizo la colecistectomía por video-laparoscopía. En el segundo (Grupo 2), se operaron 424 pacientes por una colecistectomía por mini-incisión adaptadas. Los pacientes portadores de litiaisis de la vía biliar principal fueron analizados en un tercer grupo (Grupo 3) y abordados quirúrgicamente por mini-incisiones adaptadas. Resultados: No hubo mortalidad en el grupo 1 y 2. En el tercero fallecio un paciente lo que representa el 1,18%. En relación a la morbilidad, en el primer grupo de colecistectomía por video laparoscopía hubo 63 pacientes con complicaciones (17,22%). Dentro de ellas, dos pacientes con complicaciones médicas (0,58%). Hubo 54 pacientes (14,58%) con complicaciones intra-operatorias. En las complicaciones postoperatorias hubo 7 pacientes (2,05%). El promedio de conversión a cielo abierto fue de 7,83%. En el grupo 2 de colecistectomía por mini-incisiones adaptadas, hubo 36 pacientes (9,42%) con morbilidad.

Postural restrictions in labyrintholithiasis.

Benign paroxysmal positional vertigo (BPPV) is the most frequent labyrinthopathy in humans. Treatment consists mainly of liberatory maneuvers aiming to remove otolithic debris and subsequent postural restrictions in order to prevent debris from returning into the canal. The reappearance of symptoms after an effective liberatory maneuver was studied in a group subjected to restrictions and in a second group free from restrictions. The effects of these restrictions were evaluated. No statistically significant difference was found between the groups. Accordingly, restrictions seem to have no effect upon symptom recurrence. The slight supremacy of the Semont maneuver and the prevalence of subsequent relapse compared with the Epley maneuver suggests that these maneuvers could operate on different disorders (cupulolithiasis versus canalolithiasis). Finally, late recognition of relapse in patients who undergo restrictions might even make the liberatory maneuver less effective.

Prophylaxia of cystine calculosis by alpha-mercaptopropionyl-glycine administered continuously or every other day.

We determined the efficacy of alpha-mercaptopropionyl-glycine administered in a low dosage continuously or every other day for prophylaxis of cystine calculosis. Two homozygous cystinuric patients with previous calculosis and renal unilateral hypoplasia and been given preventive treatment with alpha-mercaptopropionyl-glycine continuously administered in a low dosage (1.5-4 mg Kg-1 day-1 for 14 1/2 years and 10(-4) mg Kg-1 day-1 for 9 years respectively). Neither calculosis, nor side effects were observed. Subsequently, the patients were given 4 mg Kg-1 of the drug every second day for 1 and 1-2 years respectively without calculosis or side effect being observed. A low dosage of alpha-mercaptopropionyl-glycine(1.5-4 mg Kg-1 day-1) supplied continuously or, for a short time, 4 mg Kg-1 day-1 supplied every other day can be effective in the prophylaxis of cystine nephrolithiasis in some homozygous patients with renal unilateral hypoplasia, with lower risk of side effects.