INTRODUCTION:

Fasting during the Ramadan month is a cornerstone of Islam. Several disorders of the chronobiological rhythms occur during this month and impact on mood. Through this paper the authors provide a literature review of the impact of fasting on patients with bipolar disorders. MATERIALS AND

SUBJECTS:

A literature review using Mesh keywords through Medline database. From 1970 to 2011, articles in French and English were selected.

RESULTS:

Circadian rhythm refers to the approximately 24-hour cycles that are generated by an organism. Most physiological systems demonstrate circadian variations. Many hormones and other metabolisms, such as gastric pH, insulin, glucose, calcium and plasmatic gastrine, have been shown to exhibit circadian oscillation. The role of social rhythm in behaviors and its influence on circadian rhythms in humans is now obvious. It has been shown that the lack of concentration and irritability increased continuously during Ramadan month and reached its peak at the end of the month. Mood and vigilance are significantly decreased during the fasting month. Several authors have stated that the course of bipolar illness may be affected by the changes in social rhythm that occur during Ramadan (fasting month). Studies which have been devoted to this topic are sparse. Kadri et al., in 2000, studied 20 bipolar patients during the fasting month of Ramadan of 1417 (Hegirian calendar, corresponding to January 1997). Diagnosis of bipolar disorder was made according to ICD-10 criteria. Patients were assessed during the week before Ramadan, the second and the fourth weeks of the fasting month and the first week after its end, with the Hamilton Depression and Bech-Rafaelsen scales. The plasma concentration of lithium was also assessed. The main finding of the study was that 45% of the patients relapsed, 70% during the second week, and the remaining patients at the end of Ramadan. These relapses were not related to plasma concentration of lithium. Most of the relapses were manic (71,4%). Patients who did not relapse had more insomnia and anxiety during the second and third weeks of the study. The side effects of lithium increased and were seen in 48% of the sample, mostly dryness of the mouth with thirst and tremor. However, Farooq et al. in 2006 studied 62 bipolar patients during the fasting month of Ramadan 1427 (from 25 September to 24 October 2006). Serum lithium, electrolytes, Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were assessed, one week before Ramadan, mid Ramadan and one week after Ramadan. The side effects and toxicity were measured by symptoms and signs checklist. There was no significant difference in mean serum lithium levels at three time points. The scores on HDRS and YMRS showed significant decrease during Ramadan (F=34,12, P=0,00, for HDRS and F=15,6, P=0,000 for YMRS). Also the side effects and toxicity did not differ significantly at the three point's assessment.

CONCLUSION:

All physiologic parameters are influenced by the circadian rhythm, which is influenced in its turn by the food rhythm. So far, the results of these two main studies, with opposite results, do not help us advise bipolar patients to fast or not to fast. Other studies in this field are badly needed.

Serum levels of Phosphate (P), Calcium (Ca) and Parathyroid hormone (PTH) show circadian rhythms in healthy people. The aim of this study is to investigate whether there is also a rhythm in Hemodialysis (HD) patients.We studied 15 (11 M, 4 F) HD patients, ages were 26 - 70 (mean 53 +/- 15) years. Two of the patients had history of parathyroidectomy operation. Serum levels of phosphate, calcium, albumin and PTH were evaluated six times at 07.00, 11.00, 15.00, 19.00, 23.00 and 03.00 on the second day after scheduled HD session.The lowest serum phosphate levels were found at 15.00 (5.41 +/- 1.76 mg/dL), the highest levels were 5.97 +/- 1.77 mg/dL at 03.00. The lowest serum Ca levels were 7.90 +/- 1.31 mg/dL at 03.00, the highest levels were 8.39 +/- 1.20 mg/dL at 15.00. Serum levels of PTH increased two times in a day and then decreased. The lowest levels were 330.07 +/- 203.57 pg/mL at 07.00, the highest levels were 418.30 +/- 206.24 pg/mL at 15.00. The results of two patients who had parathyroidectomy history disclosed that the lowest levels of phosphate were 2.87 +/- 0.12 mg/dL at 15.00, the highest levels were 4.37 +/- 1.25 mg/dL at 07.00. Serum Ca levels were as; the lowest levels: 8.29 +/- 3.5 mg/dL at 03.00, the highest levels 9.30 +/- 3.50 mg/dL at 19.00. As expected, serum PTH levels were constantly low during the day disclosing no correlation with other parameters.These results show that serum P, Ca and PTH levels exhibit a circadian rhythm also in HD patients. The rhythm predominantly depends on endogen factors and intravascular volume.

The kidney chiefly maintains homeostasis of water, electrolytes, and other solutions. When kidney function is reduced, mineral metabolism is disrupted. Mineral and bone disorder in patients with chronic kidney disease associates with increased cardiovascular risk and mortality; however, management of chronic kidney disease-mineral and bone disorder in predialysis patients remains controversial. This study investigates the association between parathyroid enlargement at dialysis initiation and hyperparathyroidism management in dialysis patients. We enrolled 72 patients at dialysis initiation in this study. Using parathyroid sonography, we categorized patients based on presence (detected group; N = 18) or absence (undetected group; N = 54) of enlarged parathyroid glands and assessed the clinical characteristics and laboratory findings. A literature review of ultrasound evaluations of secondary hyperparathyroidism was conducted. Ultrasonography revealed enlarged parathyroid glands in 18 patients (25%). Serum intact parathyroid hormone levels were high in patients with enlarged parathyroid glands; however, of the 29 patients with intact parathyroid hormone levels <240 pg/mL, four had enlarged parathyroid glands. Eight of the 29 patients with serum phosphorus and calcium levels within the optimal range had enlarged parathyroid glands. Twenty of these 29 patients were followed up at 38 ± 17 months (at least 3 months): enlarged parathyroid glands were detected in 6. During follow-up, serum intact parathyroid hormone levels were significantly higher in the detected group compared with the undetected. In conclusion, enlarged parathyroid glands are frequently detected at dialysis initiation, potentially predicting the persistence of secondary hyperparathyroidism and the need for strict management.

Kidney stones are a prevalent clinical condition imposing a large economic burden on the healthcare system. Hypercalciuria remains the major risk factor for development of a Ca(2+)-containing stone. The kidney's ability to alter Ca(2+) excretion in response to changes in serum Ca(2+) is in part mediated by the Ca(2+)-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca(2+) intake and by elevated serum Ca(2+) levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca(2+) flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca(2+). This molecular mechanism likely facilitates renal Ca(2+) losses in response to elevated serum Ca(2+). Moreover, dysregulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones.

Divalent cations (calcium, magnesium, zinc, cooper, manganese) play an important role in various biological processes. Different acute or chronic renal disorders in children or adults modify the urinary excretion of these cations and may influence their concentrations in organism.Evaluation of the changes of some divalent cations levels (Cu, Zn, Mg, Ca) in acute renal diseases.We measured plasma concentrations and urinary excretion of cations in pediatric patients with acute urinary infections. We also evaluated malondyaldehide (MDA) and total antioxidant capacity (TAC) plasma levels.The obtained results show that serum levels of Ca, Cu, Zn are decreased in patients with acute urinary infections compared with a control group of healthy children, while urinary excretion of Cu and Zn there were higher in group study compared with control group. There are no significant differences of the serum magnesium concentration. Increased plasma MDA levels and decreased plasma TAC, Cu and Zn concentrations indicate an increased oxidative stress in patients with acute renal diseases.Our preliminary data show that in some acute urinary conditions, such as lower urinary tract infection and pyelonephritis, appear disturbances of plasma and urinary concentrations of divalent cations. We consi der that trace elements should be measured routinely in children with renal disorders.

Congenital hypothyroidism (CH) increases the prevalence of kidney and urogenital malformations. There are limited studies considering different aspects of kidney function in well-controlled CH patients. We evaluated some features of kidney function in euthyroid children with CH who have been receiving thyroxine hormone since early life.This cross-sectional study was conducted in Isfahan, Iran, on 74 children aged 2-15 years old (36 CH patients and 38 healthy children). Inclusion criteria for CH patients were euthyroidism at the time of the survey and initiation of replacement therapy during the early neonatal period. Kidney ultrasound evaluation was performed in all participants. Serum biochemistry included urea, creatinine, sodium (Na), potassium (K), magnesium, calcium, and cystatin C levels. Urine electrolytes, fraction excretion (FE) of electrolytes and microalbumin, and glomerular filtration rate (GFR) were also determined.The male/female ratio was 0.8/1 and 1.5/1 in the patient and control groups, respectively. Mean age and height did not differ significantly between the two groups. Ultrasound evaluation of the kidney revealed that the anteroposterior diameter of the right kidney was significantly higher in CH patients as compared to healthy subjects. No significant difference was observed between GFRs in patients with CH and healthy children. The mean values for FENa and FEK were significantly higher in the patient group.Increased FENa and FEK may be a manifestation of impaired tubular maturation in CH. More longitudinal studies are needed to evaluate kidney function in CH patients.

Due to environmental and social changes (and possibly obesity) as new risk factors for stone formation in adults and changes in imaging techniques, we assessed whether etiologies of primary pediatric urolithiasis have changed, and if relationships exist between the condition and obesity or imaging technique.All pediatric patients with documented primary urolithiasis who underwent serum and 24-hour urine analyses between 1999 and 2010 were evaluated. Age at diagnosis, gender, body mass index and imaging technique were recorded.Of the 222 patients (48% male) all had normal serum creatinine, electrolytes and minerals. Primary pediatric urolithiasis was diagnosed by ultrasound in 73% of cases and computerized tomography in 27%. Mean ± SD annual incidence of urolithiasis per 1,000 clinic visits increased from 2.4 ± 1.5 in the first half of the study period to 6.2 ± 2.1 in the second half (p <0.005). Mean ± SD age at diagnosis was 11.8 ± 3.8 years and body mass index was 21.7 ± 5.7 (rate of overweight 15%). A total of 140 patients had urine output less than 1.0 ml/kg per hour, with this being the only abnormality in 54. Hypercalciuria was observed in 46% of patients, hypocitraturia in 10% and high calcium-to-citrate ratio in 51%. Mild absorptive hyperoxaluria was noted in 3 patients and hyperuricosuria in 11, with all 14 exhibiting at least 1 additional abnormality. Cystinuria was present in 1 patient. No etiology was identified in 20 patients (9.0%).Oliguria and hypercalciuria continue to be the most common etiologies of pediatric primary urolithiasis, followed by hypocitraturia. The recent increase in stone incidence is unlikely due to increased use of computerized tomography. Incidence of obesity was not higher than in the general population. Hyperoxaluria and cystinuria are rare, and thus might not be indicated in the initial analysis.

Hypomagnesemia is a highly prevalent clinical condition affecting a large number of hospitalized patients. A decrease in systemic magnesium concentration may lead to impaired function of both neurologic and cardiovascular systems. The kidney has a pivotal role in magnesium handling by adjusting the urinary excretion of this ion in order to maintain systemic concentrations within a narrow range. As such, the cause of hypomagnesemia can be related to increments in the renal excretion of this cation. Many hypomagnesemic disorders also have characteristic changes in the renal reabsorptive capacity for other electrolytes, leading to symptoms that sometimes obscure the clinical presentation. For instance, changes in serum calcium concentration or its urinary excretion can aid in determining the underlying cause. Moreover, hypokalemia due to renal potassium losses often is associated with hypomagnesemia. Genetic defects in pathways controlling renal electrolyte transport impose the hypomagnesemic condition by facilitating renal losses. The discovery of the causative genes has greatly increased our understanding of how magnesium is transported by the kidney. Such knowledge is integral for the continued improvement of patient care with respect to bettering therapies and diagnosis.

Potassium citrate (K-Cit) is one of the medications widely used in patients with urolithiasis. However, in some cases with calcium oxalate (CaOx) urolithiasis, the significant response to alkaline therapy with K-Cit alone does not occur. There is scarce published data on the effect of magnesium chloride (Mg-Cl(2)) on urolithiasis in pediatric patients. This study aimed to evaluate the effect of a combination of K-Cit - MgCl(2) as oral supplements on urinary parameters in children with CaOx urolithiasis.This study was conducted on 24 children with CaOx urolithiasis supplements included potassium citrate (K-Cit) and magnesium chloride (Mg-Cl(2)). The serum and urinary electrolytes were measured before (phase 0) and after prescribing K-Cit alone (phase 1) and a combination of K-Cit and Mg-Cl(2) (phase 2). Each phase of therapy lasted for 4 weeks.The mean age of patients was 6.46 ± 2.7 years. Hyperoxaluria and hypercalciuria were seen in 66% and 41% of patients, respectively. Serum magnesium increased significantly during phase 2 comparing with phase 0. Urinary citrate level was significantly higher in phase 1 and 2 in comparison with phase 0, P < 0.05. In addition, urinary oxalate excretion was significantly diminished in phase 2 comparing with phase 0 and 1, P < 0.05. Soft stool was reported by 4 patients, but not severe enough to discontinue medications.These results suggested that a combination of K-Cit and Mg-Cl(2) chloride is more effective on decreasing urinary oxalate excretion than K-Cit alone. The Iranian Clinical Trial registration number IRCT138707091282N1.

TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel that is regulated by serum Mg(2+) concentrations. Changes in Mg(2+) concentration have been shown to alter cell proliferation in various cells; however, the mechanism and the ion channel(s) involved have not yet been identified. Here we demonstrate that TRPM7 is expressed in control and prostate cancer cells. Supplementation of intracellular Mg-ATP or addition of external 2-aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM currents, suggesting that these currents are dependent on TRPM7. Importantly, although an increase in the serum Ca(2+)/Mg(2+) ratio facilitated Ca(2+) influx in both control and prostate cancer cells, a significantly higher Ca(2+) influx was observed in prostate cancer cells. TRPM7 expression was also increased in cancer cells, but its expression was not dependent on the Ca(2+)/Mg(2+) ratio per se. Additionally, an increase in the extracellular Ca(2+)/Mg(2+) ratio led to a significant increase in cell proliferation of prostate cancer cells when compared with control cells. Consistent with these results, age-matched prostate cancer patients also showed a subsequent increase in the Ca(2+)/Mg(2+) ratio and TRPM7 expression. Altogether, we provide evidence that the TRPM7 channel has an important role in prostate cancer and have identified that the Ca(2+)/Mg(2+) ratio could be essential for the initiation/progression of prostate cancer.