Frequency of PAH Mutations Among Classic Phenylketon Urea Patients in Mazandaran and Golestan Provinces, North of Iran.

BACKGROUND: Phenylketonuria (PKU) is the most common aminoacidopathy with an autosomal recessive inheritance pattern. A global PKU prevalence is estimated about 6.002 in 100,000 newborns. In Iran, the prevalence of PKU is estimated at about 1 in 4,698, and it shows an increasing trend from north (0.0015%) to south (0.02%) of the country. Untreated PKU causes mental retardation, microcephaly, and seizure. PAH gene mutations located at chromosome 12q23 are responsible for the classical type of this disease. The spectrum of PAH mutations is varied in different ethnicities and different parts of the world. The aim of this study was to investigate the frequency of PAH mutation in the Mazandaran province, which could be useful for genetic counseling and prenatal diagnosis. METHODS: A total of 66 individuals from 33 families from two provinces (9 families from Golestan and 24 families from Mazandaran) from north of Iran participated in this study. After genomic DNA extraction, PAH gene analysis was carried out using DNA sequencing of both coding and non-coding regions by ABI 3130XL genetic analyzer. RESULTS: Twenty-six different mutations were identified in the PAH gene in this study. Four mutations including IVS10-11 (c.1066-11G>A), c.727C>T (p.Arg243X), c.898G>T (p.Ala300Ser), and c.601C>T (p.His201Tyr) were the most common mutations with 37.48% frequency in Mazandaran province. Most frequent mutations in Golestan province were IVSI0-11 (c.1066-11G>A), c.722delG (p.Arg241fs), c.842C>T (p.Pro281Leu), and IVSII+5 (G>A) with frequency 58.57%. CONCLUSIONS: The results from the present study verify heterogeneity of the PAH gene and may help to diagnose tests for carrier detection and prenatal diagnosis of the PKU disease in Iranian population.

The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial

Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy (DN), however in a substantial number of patients, progression of renal disease are not completely halted by these agents. We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system. The dosage of PTX used in our trial was at a low dosage of 400mg daily and to our knowledge, we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage. One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were randomly assigned to two groups. Control group (n=50, 26 males and 24 females) received losartan and enalapril, while treatment group (PTX Group) (n=50, 28 males and 22 females) was given losartan, enalapril and pentoxifylline 400mg/day for 6 months. At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine, HbA1c, blood pressure and urinary protein excretion between two groups (P>.05). In the PTX group, the mean rate of (..) (AU)

Aunque el bloqueo del sistema renina-angiotensina ha sido citado como el tratamiento inicial para la nefropatía diabética (ND), en un número significativo de pacientes el avance de la enfermedad renal no se ve frenado en su totalidad por estos agentes. Hemos realizado un ensayo clínico doble ciego para valorar el efecto acumulativo de la pentoxifilina (PTX) en la reducción de la proteinuria en pacientes con diabetes tipo 2 (DM2) con bloqueo del sistema de angiotensina. La dosis de PTX utilizada en nuestro ensayo fue una cantidad baja de 400 mg diarios y, en nuestra experiencia, no logramos encontrar ningún artículo que evaluara el efecto antiproteinúrico de la PTX con esta dosis. De forma aleatoria, se dividieron en dos grupos 100 pacientes con ND y proteinuria persistente a pesar del tratamiento con losartán y enalapril durante al menos tres meses antes de ser incluidos en el estudio. El grupo de control (n = 50, 26 hombres y 24 mujeres) fueron tratados con losartán y enalapril, mientras que el grupo de tratamiento (grupo de PTX: n = 50, 28 hombres y 22 mujeres) recibieron losartán, enalapril y 400 mg/día de pentoxifilina durante 6 meses. Al comienzo del estudio no se encontraron diferencias significativas en las (..) (AU)

The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial.

Although blockade of renin-angiotensin system have been cited as the first line of therapy for the management of diabetic nephropathy (DN), however in a substantial number of patients, progression of renal disease are not completely halted by these agents. We have conducted a double blinded clinical trial to assess the additive effect of pentoxifylline on reduction of proteinuria among patients with type 2 DM under blockade of angiotensin system. The dosage of PTX used in our trial was at a low dosage of 400mg daily and to our knowledge, we did not found article which evaluated the antiproteinuric effect of pentoxifylline in this dosage. One hundred patients with DN and persistent proteinuria despite treatment with losartan and enalapril in at least 3 months before inclusion in the study were randomly assigned to two groups. Control group (n=50, 26 males and 24 females) received losartan and enalapril, while treatment group (PTX Group) (n=50, 28 males and 22 females) was given losartan, enalapril and pentoxifylline 400mg/day for 6 months. At the beginning of the study there were no significant differences in demographic and clinical characteristics of patients including serum creatinine, HbA1c, blood pressure and urinary protein excretion between two groups (P>.05). In the PTX group, the mean rate of urinary protein excretion have significantly decreased from 616.66mg to 378.24 after 3 months (P=.000) and to 192.05mg after 6 months (P=.000) whereas no significant changes were observed in the control group. The beneficial antiproteinuric effect of PTX was not associated to the degree of metabolic control and a reduction of blood pressure. In addition, at the end of study, the mean clearance of creatinine was significantly higher in PTX group (P=.04). In conclusion, PTX can significantly provide additive antiproteinuric effect and slow the decrease in GFR among patients with type 2 DM under blockade of angiotensin system.

Effect of intranasal DDAVP in prevention of hypotension during hemodialysis.

INTRODUCTION: The development of intradialytic hypotension during hemodialysis (HD) in which fluid removal is the primary goal, contributes to the excessive morbidity that is associated with the dialysis procedure. MATERIALS AND METHODS: In a double blinded clinical trial, we compared the possible effect of intranasal DDAVP with intranasal distilled water as a placebo in prevention of intradialytic hypotension (IDH) in patients with known symptomatic IDH. In the first month of the study, nasal spray of distill water were administrated 30 minutes before all HD session (Placebo Group, Group 1) and then after a 30-day washout period we were used intranasal DDAVP 30 minutes before HD session (Vasopressin Group, Group 2). Blood pressure was measured just before HD, two hours later and after termination of HD. A hypotensive episode was defined as a decline of systolic blood pressure of more than 10mm Hg. RESULTS: In overall Seventeen patients (nine men, eight women; mean age, 47.5 years) with known symptomatic IDH were enrolled in the study. The kind of dialysis membranes, mean of blood flow rate, dialyzate flow rate and ultrafiltration rate were the same in both groups. Each group has 204 HD session (17 * 12). Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). CONCLUSION: These results indicate that Compared with placebo, Vasopressin is significantly associated with a decreased incidence of intradialytic hypotension episodes during hemodialysis.

Effect of Intranasal DDAVP in Prevention of Hypotension during Hemodialysis

Introduction: The development of intradialytic hypotension during hemodialysis (HD) in which fluid removal is the primary goal, contributes to the excessive morbidity that is associated with the dialysis procedure. Materials and Methods: In a double blinded clinical trial, we compared the possible effect of intranasal DDAVP with intranasal distilled water as a placebo in prevention of intradialytic hypotension (IDH) in patients with known symptomatic IDH. In the first month of the study, nasal spray of distill water were administrated 30 minutes before all HD session (Placebo Group, Group 1) and then after a 30-day washout period we were used intranasal DDAVP 30 minutes before HD session (Vasopressin Group, Group 2). Blood pressure was measured just before HD, two hours later and after termination of HD. A hypotensive episode was defined as a decline of systolic blood pressure of more than 10mm Hg. Results: In overall Seventeen patients (nine men, eight women; mean age, 47.5 years) with known symptomatic IDH were enrolled in the study. The kind of dialysis membranes, mean of blood flow rate, dialyzate flow rate and ultrafiltration rate were the same in both groups. Each group has 204 HD session (17 * 12). Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). Conclusion: These results indicate that Compared with placebo, Vasopressin is significantly associated with a decreased incidence of intradialytic hypotension episodes during hemodialysis (AU)

Introduction: The development of intradialytic hypotension during hemodialysis (HD) in which fluid removal is the primary goal, contributes to the excessive morbidity that is associated with the dialysis procedure. Materials and Methods: In a double blinded clinical trial, we compared the possible effect of intranasal DDAVP with intranasal distilled water as a placebo in prevention of intradialytic hypotension (IDH) in patients with known symptomatic IDH. In the first month of the study, nasal spray of distill water were administrated 30 minutes before all HD session (Placebo Group, Group 1) and then after a 30-day washout period we were used intranasal DDAVP 30 minutes before HD session (Vasopressin Group, Group 2). Blood pressure was measured just before HD, two hours later and after termination of HD. A hypotensive episode was defined as a decline of systolic blood pressure of more than 10mm Hg. Results: In overall Seventeen patients (nine men, eight women; mean age, 47.5 years) with known symptomatic IDH were enrolled in the study. The kind of dialysis membranes, mean of blood flow rate, dialyzate flow rate and ultrafiltration rate were the same in both groups. Each group has 204 HD session (17 * 12). Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). Conclusion: These results indicate that Compared with placebo, Vasopressin is significantly associated with a decreased incidence of intradialytic hypotension episodes during hemodialysis (AU)