High Purine Diet Research Articles

The flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. ameliorates renal oxidative stress and inflammation in uric acid nephropathy rats through promoting uric acid excretion

Uric acid metabolic disorder is considered to be the main pathogenesis of uric acid nephropathy (UN). Smilax glabra Roxb. is a traditional Chinese herb which has been used in the treatment of gout, but the mechanism was unclear. In this study, we investigated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on uric acid nephropathy rats and its underlying mechanisms of promoting uric acid excretion. Sprague Dawley (SD) rats were induced by high purine diet (yeast pellets + adenine) for 5 weeks. Rats were orally treated with SGF or allopurinol daily. The biochemical parameters and enzymes in different treated rats were determined by commercial kits. Kidney pathology was visualized using optical microscopy and electron microscopy. Renal inflammatory factors were detected by ELISA. Renal fibrosis factors and uric acid transporters were analyzed by real time RT-PCR and western blot. The results showed that SGF significantly improved kidney function. Histopathologic examination revealed that urate-induced renal damage was markedly reversed by SGF. Meanwhile, SGF treatment was also found to significantly inhibit renal oxidative stress. SGF treatment obviously suppressed the inflammatory factors of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and the profibrotic factors of basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) expression in UN rats. Moreover, SGF either significantly inhibited uric acid production or promoted uric acid excretion in UN rats. The mechanism of SGF promoting uric acid excretion was related to its increase of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1), organic anion transporters 2 (OCT2) and organic cation/carnitine transporters 2 (OCTN2) expression. In conclusion, SGF could ameliorate renal oxidative stress and inflammation in UN rats through promoting uric acid excretion.

Adaptive evolution to a high purine and fat diet of carnivorans revealed by gut microbiomes and host genomes

Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible with high purine and fat metabolism based on analysis of host genomes and symbiotic gut microbial metagenomes. We found that the gut microbiomes of carnivorous Carnivora (e.g., Felidae, Canidae) clustered in the same clade, and other clades comprised omnivorous and herbivorous Carnivora (e.g., badgers, bears and pandas). The relative proportions of genes encoding enzymes involved in uric acid degradation were higher in the gut microbiomes of meat-eating carnivorans than plant-eating species. Adaptive amino acid substitutions in two enzymes, carnitine O-palmitoyltransferase 1 (CPT1A) and lipase F (LIPF), which play a role in fat digestion, were identified in Felidae-Candidae species. Carnivorous carnivorans appear to endure diets high in purines and fats via gut microbiomic and genomic adaptations.

Optimization Of Elevating Blood Uric Acid Levels With High Purine Diet

Exploration of the use of medicinal plants to lower uric acid levels has been widely practiced. Stages of new drug development research is a preclinical test using experimental animals, therefore the manufacture of an animal model of hyperuricemia is necessary. This study aims to determine the optimal induction of uric acid to increase blood uric acid levels by administering high purine foods such as cow’s liver, cow’s spleen, Gnetum gnemon , emping and fried peanuts. Eighty male white rats were used individuals to be divided into 4 groups, they were: (I) cow’s liver, (II) cow’s liver and cow’s spleen, (III) cow’s liver, cow’s spleen and boiled gnetum gnemon beans, and (IV) cow’s liver, cow’s spleen, emping and fried peanuts. This study using easy touch GCU to measure blood uric acid level. The result of statistical analysis of uric acid level means with 5 times repetition using One Way ANOVA showed that there was a very significant difference between treatments ( p <0,01). The results concluded that high purine diet in group I, II and III had not been able to increase uric acid levels significantly. High purine diet group IV was able to increase blood uric acid levels significantly to make the rats experiencing hyperuricemia with the level of 6.54 mg/dL on day 7 and 13.79 mg/dL on day 14.

Green Tea Extract (Camellia sinensis L.) Effects on Uric Acid Levels on Hyperuricemia Rats (Rattus norvegicus)

Uric acid is the end product of purine degradation. When uric acid levels exceed normal limits, it will build up and cause hyperuricemia. Allopurinol is one of the most effective and common medicine for hyperuricemia, but it brings serious side effects, therefore it is needed alternative therapy for hyperuricemia. One plant that may be expected to low uric acid levels is green tea ( Camellia sinensis L.), that contains many antioxidants polyphenols, especially flavonoids. Flavonoid has strong antioxidant properties, act as free radical and metal scavengers, and also xanthine oxidase (XOD) inhibitors. This study investigates the potential of green tea using various doses of 150 mg/kg, 300 mg/kg, and 600 mg/kg of body weight in 24 white male rats ( Rattus norvegicus ) Wistar strain that has been received high purine diet in 60 consecutive days. This study used DHBSA methods to measure uric acid levels in blood serum and urine that excreted 8 hours before surgery. Green tea extract that contains polyphenol can inhibit XOD activities, therefore, it leads to decrease uric acid level in blood and increase the excretion through urine by modulating urate gene transporter. A therapy with 600 mg/kg body weight of GTE is the most effective dose to decrease uric acid levels in serum and to increase excretion of exceeding uric acid significantly (p < 0.01), from One Way ANOVA and Tukey analysis.

Effects of Clostridium butyricum on serum uric acid and inflammatory mediators in rats with hyperuricemia

To investigate the effects of intragastric administration of Clostridium butyricum in regulating serum uric acid, lipopolysaccharides (LPS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with hyperuricemia rats. Forty SD rats were randomized into 4 equal groups, namely the normal control group, hyperuricemia model group, benzbromarone (3 mg/kg daily) intervention group and live Clostridium butyricum group (1.5×107 CFU/day). Except for those in the control group, the rats were subjected to intragastric administration of yeast extract and oteracil potassium once daily for 12 weeks to induce hyperuricemia with corresponding treatments. The changes in serum uric acid, lipopolysaccharides , IL-6 and TNF-α in each group were detected. The serum level of uric acid was significantly higher in rats fed with high-purine diet than in the control rats (P<0.01), demonstrating the successful establishment of hyperuricemia models. In rats with hyperuricemia, serum uric acid level was positively correlated with the levels of LPS, IL-6 and TNF-α, and their serum levels decreased significantly and progressively with time in Benzbromarone group and Clostridium butyricum group. Benzbromarone was more effective in decreasing serum uric acid in the rats, while Clostridium butyricum produced a stronger effect in down-regulating the inflammatory mediators. Chronic inflammatory reaction exists in rats with hyperuricemia. Intragastric administration of Clostridium butyricum can effectively decrease serum uric acid level and inhibit the inflammatory cytokines, and thus contributes to immune homeostasis in the intestines.

Patients with gout differ from healthy subjects in renal response to changes in serum uric acid

ObjectiveOur objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects. MethodsFEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test. ResultsAnalysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours. ConclusionThese observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout.

Rats hyperuricemia model established by lipid emulsion simulating irregular of diet

Due to the irregular of diet and overfeeding greasy and surfeit flavor closely associated with hyperuricemia disease, the lipid emulsion containing high cholesterol was used to model. To obtain a more stable and sustained animal model for the efficacy evaluation of traditional Chinese herbs, we observed the influence on the serum uric acid of rat induced by the lipid emulsion compared with high purine diet. 36 SD male rats were randomized to the normal control group, high purine diet group and lipid emulsion group respectively. The general behavior, body weight and daily food intake of rats were observed. The orbital blood was taken to separate into the serum and 24 hours urine was collected. The serum indexes such as UA, BUN, Cr, ALT, AST, TC, TG, LDL-c were determined every 2 weeks, and XOD, ADA enzyme activity were determined at the 4th week. The urine indexes such as UA, Cr and Cua/Ccr were determined at the 4th week. After stopping modeling, the serum UA were determined two weeks and four weeks later respectively. At the 2nd week, the body weight and daily food intake of rats in the lipid emulsion group reduced significantly, and the level of serum UA, BUN, Cr, TC, LDL-c, ATL, AST raised significantly meanwhile TG reduced. At the 4th week, the serum UA in high purine diet group did not raise, and the serum XOD raised obviously while ADA did not; the serum UA in lipid emulsion group was higher significantly, and the serum XOD and ADA raised while Cua/Ccr reduced obviously. At the 6th weeks, the serum UA in both the high purine diet group and lipid emulsion group raised obviously. After stopping modeling, the serum UA in lipid emulsion group still maintained a high level at the 2nd week and back to the normal level at the 4th week. Compared with high purine diet, the hyperuricemia model induced by lipid emulsion forms earlierand more stable. It maybe has great value to study the pharmacodynamics of traditional Chinese medicine treatment to hyperuricemia disease. Its mechanism may be related to increasing XOD and ADA enzyme activity which can promote uric acid synthesis, meanwhile inhibiting of uric acid excretion.

XANTHINE OXYDASE INHIBITION OF KOMBUCHA TEA IN HYPERURICEMIA INDUCED WISTAR RAT: decrease of uric acid, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine

Background: Hyperuricemia is a condition of high level of uric acid in the body due to distortion of purine nucleoside metabolism through hipoxanthin, xanthin, and guanin of basic purine. Objective: to find a cure of hyperuricemia base on the utilization of kombucha tea. Methods: This is a true experimental study by applying posttest only control group design to determine whether kombucha tea inhibit xanthine oxidase in hyperuricemic induced rat reveales by decrease of uric acid, malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG). In this study, hyperuricemia rat was achieved by intake of high purine diet. Rats were fed with a mixture of 4 g/kg BW of Gnetum gnemon with 50 mL/kg BW of chicken liver ad libitum for 9 days. Treatments in this research are combination of fermentation time of Kombucha tea and volume of this tea, i.e fermentation time 4, 8, and 12 days and the volume are 1 mL and 4 mL. Therefore, there would be seven groups of treatment including control group. ANOVA was then applied to determine the treatment effect with p < 0.05 was concidered significant. Results: This study indicates that kombucha tea has an ability to inhibit xanthine oxidase in hyperuricemic induced rat and decrease uric acid, MDA, and 8-OHdG. This ability was achieved with combination treatment of 12 days fermentation and 4 mL of kombucha intake. Xanthine oxidase, uric acid, MDA, and 8-OHdG levels by this treatment were obtained significantly lower compare to control group. Conclusion: This study proved that kombucha tea was potent to cure hyperuricemia of wistar rat via inhibition of xanthine oxidase produced.

Effects of chicory inulin on serum metabolites of uric acid, lipids, glucose, and abdominal fat deposition in quails induced by purine-rich diets.

Inulin, a group of dietary fibers, is reported to improve the metabolic disorders. In the present study, we investigated the effects of chicory inulin on serum metabolites of uric acid (UA), lipids, glucose, and abdominal fat deposition in quail model induced by a purine-rich diet. In this study, 60 male French quails were randomly allocated to five groups: CON (control group), MOD (model group), BEN (benzbromarone-treated group), CHI-H (high-dosage chicory inulin-treated group), and CHI-L (low-dosage chicory inulin-treated group). The serum UA level was significantly increased in the model group from days 7 to 28, as well as triglyceride (TG) and free fatty acid (FFA) increased later in the experimental period. The abdominal fat ratio was increased on day 28. Benzbromarone can decrease UA levels on days 14 and 28. The high and low dosage of chicory inulin also decreased serum UA levels on days 7, 14, and 28. The abdominal fat ratio, activity, and protein of acetyl-CoA carboxylase (ACC) were decreased in chicory inulin-treated groups. The activities of xanthine oxidase (XOD) and fatty acid synthase (FAS) were increased in the model group and decreased in the benzbromarone and chicory inulin groups. This study evaluated a quail model of induced hyperuricemia with other metabolic disorders caused by a high-purine diet. The results indicated that a purine-rich diet might contribute to the development of hyperuricemia, hypertriglyceridemia, and abdominal obesity. Chicory inulin decreased serum UA, TG, and abdominal fat deposition in a quail model of hyperuricemia by altering the ACC protein expression and FAS and XOD activities.

Pola makan, obesitas, dan frekuensi serangan pada pasien artritis gout

Background: Trend of gout arthritis prevalence is increasing every year. Obesity, high purine diet, especially from an animal source, are some risk factors for recurrent gout attacks.Objective: To evaluate the relationship between diet, obesity, and frequency of gout flares in gout arthritis patients.Method: This study was a cross-sectional study with patients from RSUP Dr. Sardjito, RSUD Wirosaban, RSUD Panembahan Senopati that ever diagnosed as gout arthritis within February 2010 - February 2012 which can be seen in the medical record and live in Special District of Yogyakarta with the full address provided, as the respondents of this study. The home visit was done for dietary assessment, waist circumference measurement, and interviewing the respondent about gout flares frequency during the last year.Results: Vitamin C consumption in the 1st and 2nd tertiles increase the odds to have any gout flare (OR=5.5; 95% CI: 1.08-27.77 and OR=1.5; 95% CI: 0.29-7.35, respectively). Obesity tends to increase the odds of having any gout flares up to 1.4 times (95% CI: 0,38-5,25).Conclusion: Low consumption of vitamin C significantly increases the odds of having any gout flares. The odds is also higher in patients with obesity, though this relationship is statistically insignificant.

A Case of Hereditary Xanthinuria Type 1 Accompanied by Bilateral Renal Calculi

Hereditary xanthinuria is an extremely rare purine metabolism disorder caused by a genetic abnormality in xanthine dehydrogenase. A new case of hereditary xanthinuria type 1 accompanied by bilateral renal calculi was encountered. We performed an allopurinol loading test and diagnosed classical type 1 xanthinuria. Through genetic diagnosis, we identified a mutation site in the xanthine dehydrogenase gene. Genetic analysis revealed a homozygous deletion of cytosine 2,567 in the xanthine dehydrogenase gene, and as a result, a stop codon was formed at position 928. Renal failure caused by the deposition of xanthine crystals is a known complication because xanthine is poorly soluble in water. With high fluid intake and low purine diet, no significant increase in calculi has been observed in this patient for 2 years.

Mineralogical and morphological investigation of kidney stones of a Mediterranean region (Basilicata, Italy)

Kidney stones are a very frequent finding in southern Italy, but stone analysis is not routinely performed. However, it is an important requirement not only for a successful treatment of this disease, but also for the prophylaxis to prevent any recurrence. We therefore set out to analyze 80 kidney stones collected from Basilicata Region (Southern, Italy). X-ray powder diffraction as well as optical and scanning electron microscopy and petrographic thin section analysis have been applied in order to determine the mineralogical and morphological compositions. The internal structure and the relation between major and minor components have facilitated the classification of the kidney stones according to a detailed scheme. As it is known from other country, calcium oxalate stones were the most frequent (59%) [39% mainly composed of whewellite, CaC₂O₄*H₂O and 29% is mainly made of weddellite, CaC₂O₄*2H₂O]. Uric acid stones were abundant too (18%). Calcium phosphate and cystine stone were less. The results of the observations of kidney stones in thin petrographic sections led to the identification of more cores in the same whewellite kidney stones. In some kidney stones the core is not situated in the central zone, which represents the point of attachment on kidney wall. Basilicata kidney stone prevalence is different from the average prevalence determined in other Mediterranean areas. The comparison showed that calcium oxalate stones seem to be more frequent, and there is a high prevalence of uric acid kidney stones and a lower prevalence of phosphate kidney stones, especially hydroxyapatite. The relative increase frequency of uric acid stones in the northern part of the Region may be due to high-purine diets and softness water consumption.

Impact of rosiglitazone on uric acid metabolism and its mechanism

Objective To observe whether high-level insulin increases serum uric acid level and rosiglitazone improves hyperuricemia, and to explore the mechanism. Methods OLETF rats with spontaneous type 2 diabetes complicated with metabolic syndrome and normal control LETO rats were randomly divided into three groups (n=20 each). The animals were fed with standard chow diet in control group, high-purine diet and adenine administered intragastrically in experimental group, and rosiglitazone in interventional group. Body weight, serum levels of uric acid, insulin, triglyceride ( TG ) , and total cholesterol ( TC ) were measured after 3 weeks. Urate transporter 1 ( URAT1 ) and uric acid transporter (UAT) mRNA expressions in renal cortex were examined. HK-2 cells were incubated with various concentrations of insulin for 24 hours. UAT mRNA expression in HK-2 cells was examined. Results ( 1 ) In control group, the insulin level of OLETF rats was significantly higher than that of LETO rats ( P<0. 05 ), and there was no significant difference in serum uric acid level between OLETF and LETO rats. (2)In experimental groups, the insulin level in OLETF rats was significantly higher than that in LETO rats [(61.83±12.13 vs 36.73±12.73 )μIU/ml ,P<0. 05], and the incidence of hyperuricemia (76.92% vs 36.13%,P<0.01 ) and serum uric acid level[( 327.75 ±45.73 vs 264.40±36.32 ) μmol/L, P<0. 01]in OLETF rats were significantly higher than those in LETO rats. (3) Insulin[(41.3± 10.2 vs 61.8±12. 1 )μIU/ml,P<0. 05]and uric acid[( 198.0±45.4 vs 236.9±29.30 ) μmol/L, P<0. 05]levels in OLETF rats in interventional group were significantly lower than those of OLETF rats in experimental group, meanwhile the amount of urinary uric acid excretion was significantly increased[(5 644±371 vs 4 692±278 ) μ mol/L, P<0. 05]. (4) There was no significant difference in insulin level and the expressions of URAT1 and UAT mRNA in renal cortex between OLETF rats in control group and experimental group. URAT1 mRNA expression of OLETF rats in interventional group was significantly decreased, while UAT mRNA expression was significantly increased. (5)With the increase of insulinconcentration in culture medium, the expression of UAT mRNA expression in HK-2 cells was gradually decreased. Conclusions Rosiglitazone may alleviate hyperinsulinemia-induced hyperuricemia via regulating UAT and URAT1 mRNA expression. Key words: Rosiglitazone; Insulin; Hyperuricemia; Urate transporter 1; Uric acid transporter

Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions

Insulin resistant Otsuka-Long-Evans-Tokushima Fatty (OLETF) and its control Long-Evans Tokushima Ohtsuka (LETO) rats were used to generate a model for acute hyperuricemia. Upon the onset of insulin resistance OLETF rats were feed with high-purine diet, and the development of acute hyperuricemic renal injury and gouty-like lesions was monitored. Rosiglitazone was also administered to demonstrate whether improved insulin sensitivity would prevent high-purine diet induced renal injury and gouty-like lesions. Otsuka-Long-Evans-Tokushima Fatty rats showed significant higher incidence of hyperuricemia as compared to the control LETO rats (77 vs. 36.1%, P < 0.05), indicating that insulin resistance exacerbates the development of hyperuricemia following high-purine load. Consistent with this observation, improvement of insulin sensitivity by administration of rosiglitazone significantly reduced high-purine diet induced renal injury and gouty-like lesions. It was found that insulin resistance is associated with impaired capability for maintaining the homeostasis of renal uric acid excretion and reabsorption. Upon high-purine load, insulin resistance enhances urate reabsorption as manifested by up-regulated URAT1 expression and reduces urate excretion as characterized by down-regulated UAT expression. Our data demonstrated strong evidence indicating that insulin resistance acts as an independent risk factor predisposing OLETF rats more susceptible to the development of hyperuricemia and gouty arthritis following high-purine load.

Uric acid in Parkinson's disease

Recent studies have provided evidence that uric acid may play a role in the development and progression of Parkinson's disease (PD). Uric acid is a natural antioxidant that may reduce oxidative stress, a mechanism thought to play a role in the pathogenesis of PD. Higher levels of serum urate (SU) may have a neuroprotective effect. High SU levels reduced the risk of developing PD and correlated with slower PD progression. Among PD patients SU levels were lower as compared with controls. The manipulation of SU levels holds promise in the treatment of PD. It is possible that a high purine diet in patients with PD may slow progression of the disease. Milk and meat consumption as well as exercise modify the risk of developing PD possibly through their influence on SU levels. In this article, we review the association between PD and SU levels and its implication on the management of PD.

Clinical Quiz

A 3.5-year-old boy was admitted because of fever and urinary symptoms. He was the first offspring of his healthy first-cousin parents, with a normal birth weight. After 2 months of breastfeeding, he was placed on formula milk. At 7 months of age, he had been admitted because of urinary-tract infection (UTI), failure to thrive (FTT), and steatorrhea. Radiological study showed a stone in his left kidney. His UTI was treated with antibiotics but his parents refused more studies. This time, he had steatorrhea and FTT (weight, height, and head circumference below the 5th percentile). In physical examinations, his heart and lungs were normal and there was no organomegaly or lymphadenopathy, but we did notice diminished deep-tendon reflexes. Further studies showed normal sweat test; urine white blood cells (WBC), 25 cells/high-power field; urine bacteria, >105/ml; serum WBC, 7200 cells/μl; Hg, 10.7 g/dl; prothrombin time (PT) activity, 84%; serum cholesterol, 28 mg/dl (45-82 mg/dl); triglyceride, 9 mg/dl (30-86 mg/dl); low-density lipoprotein, 16 mg/dl (60-140 mg/dl); high-density lipoprotein, 10 mg/dl (35-55 mg/dl). His parents lipoprotein profiles were normal. His peripheral blood smear and intestinal biopsy are shown in Figures 1 and 2. Meanwhile, his voiding cystouretherogram was normal and in radiologic study he had two stones in his left kidney. His UTI was treated with antibiotics and lithotripsy was done. The stone analysis showed a mixed stone of uric acid, calcium oxalate, and triple-phosphate.FIG. 1: Acanthocytes in peripheral blood smearFIG. 2: Lipid laden enterocytes in intestinal biopsyWhat is the diagnosis? A. Intestinal lymphangiectasia B. Cystic fibrosis C. Anderson's disease D. Abetalipoproteinemia E. Schwachman-Diamond syndrome F. Celiac disease ANSWER/DISCUSSION ANSWER: Abetalipoproteinemia (ABL). In fact, in lipoprotein electrophoresis there was an absence of apolipoprotein B. COMMENT: ABL is a rare autosomal recessive disorder caused by mutation in the gene of microsomal triglyceride transfer protein, which transfers lipids to apolipoprotein B (apoB). Abnormality in this protein will cause a virtual absence of apoB-containing lipoproteins [chylomicron, very-low-density lipoprotein (VLDL), (LDL)] and extremely low levels of triglyceride and cholesterol. Inability of intestinal enterocytes to secrete long-chain fatty acids into the blood will lead to an accumulation of lipids in the enterocytes (lipid-laden enterocytes), malabsorption of lipids and fat-soluble vitamins, steatorrhea, and FTT. In fact, most of the symptoms of ABL are due to vitamin deficiency, especially vitamin E. These findings are: bizarrely shaped red blood cells (acanthocytes) and mild anemia; neurologic problems starting with diminished deep-tendon reflexes, followed by gradual loss of distal lower-extremity vibratory and proprioception senses; dysmetria; ataxia, and spastic gait, and ophthalmologic problems (decreased night and color vision, progressive retinitis pigmentosa). Diagnosis is made by extremely low levels of cholesterol, triglyceride, VLDL, LDL, and apoB. Therapy includes avoidance of long-chain fatty acids and administration of fat-soluble vitamins. (1) On the other hand, hyperoxaluria and subsequent oxalate lithiasis can be due to increased oxalate production or absorption. Ca2+ in the intestinal lumen, by binding to oxalate and forming insoluble salts, decreases absorption of oxalate. In ABL (as in other fat-malabsorption disorders), excessive amounts of fat in the colon combine with Ca2+, leading to lower oxalate salt formation and increased oxalate absorption. This will lead to hyperoxaluria and oxalate stone formation. (2) Uric acid is responsible for formation of another type of kidney stone. The main determinant factor of uric acid supersaturation in the urine and subsequent stone formation is low urine pH. Decreased urine volume, high-purine diet, or increased endogenous uric acid production are other causes of uric acid stone formation. Unabsorbed dietary fatty acids in the intestinal lumen can cause an osmotic diarrhea and patients with chronic diarrhea are particularly at risk from uric acid stones, because they are often dehydrated, so they have a chronic metabolic acidosis and acidic urine. They also have lower urine volume. The dimensions of uric acid crystals closely match those of calcium oxalate and it has been suggested that the uric acid crystals promote heterogeneous nucleation of calcium. Finally, obstruction of urinary system by stones and subsequent stasis would be a risk factor for UTI and, in the presence of urea-splitting bacteria, urea and H+ could form triple-phosphate stones. (3) Two other inherited disorders that affect apoB-containing lipoproteins are Anderson's disease and familial hypobetalipoproteinemia. In Anderson's disease, only apoB48 is absent and acanthosytosis is rare. Familial hypobetalipoproteinemia is an autosomal co-dominant disorder. Patients with homozygous familial hypobetalipoproteinemia have exactly the same clinical picture as patients with ABL, but their parents, who are heterozygotes, have plasma concentrations of apoB and LDL that are one-quarter to one-half the normal levels.

Gout and Hyperuricemia

Gout is recognized by sudden onsets of joint pain and swelling caused by imbalances in production and excretion of uric acid. Hyperuricemia is a risk factor for gout, however, not all patients with hyperuricemia will develop gout. Other risk factors include hypertension, renal insufficiency, obesity, excessive alcohol consumption, high purine diets, and medications such as thiazide diuretics and low dose aspirin. Management of gout and hyperuricemia can be achieved through inhibiting urate synthesis, enhancing urate excretion, or both. Medications to treat gout include NSAIDs, colchicine, and glucocorticosteroids. Chronic therapy with uricosuric agents or xanthine oxidase inhibitors may be necessary for those with recurrent attacks.

Effects of energy and purines in the diet on proliferation, differentiation, and apoptosis in the small intestine of the pig

The effects of the energy and purine content in the diet on mucosal cell mitosis, function, and apoptosis in the small intestine of pigs were investigated in two experiments. In experiment I, three groups of five pigs were first fed a commercial diet that contained 9.1 MJ metabolizable energy (ME) per kilogram dry matter (DM) and 16.4% crude protein. It was followed by the experimental diets for 5 days each starting with an energy deficit (5.8 MJ ME/kg DM; 7% crude protein) followed by a high-energy diet with low purine content (14.1 MJ ME/kg DM; 13.6% crude protein; 460 mg purines/kg), or alternatively an isocaloric high-purine diet (2,160 mg purines/kg). During experimental periods, blood samples were drawn daily through catheters for insulin-like growth factor-I (IGF-1) determination. The animals were killed at the end of the corresponding feeding period and gut tissue samples were collected. In tissue samples, IGF-1 and parameters for the characterization of mitosis (thymidine kinase [TK], proliferating-cell nuclear antigen (PCNA]) and differentiation (RNA content, alkaline phosphatase, sucrase) were measured. The degree of apoptosis was determined histologically. In experiment II, five pigs were fitted with simple T-cannula at the distal jejunum. They were fed the three experimental diets consecutively for 7 days each and sucrase and alkaline phosphatase were measured in digesta (four samples daily). IGF-I in blood but not in tissue clearly responded to the energy content of the diet with a decrease during the deficit and an increase in the two high-energy groups. However, purines had no additional effect on IGF-I. TK, PCNA, and gut weight showed an energy effect on mitosis, which was paralleled by increased peripheral IGF-I. Purines led to a further increase of mitosis, but IGF-I and gut weight were not increased. The degree of mitosis was correlated with higher activities of sucrase and alkaline phosphatase and also with the number of apoptotic cells. The enzyme activity increased from the deficit to the high-energy group and was further elevated due to purines. The results from experiment II also confirm these effects of energy and purines, because the activities of the enzymes in digesta decreased during energy deficit, but increased due to energy and in addition to purines.

The management of gout.

We now have sufficient knowledge to be able to identify the factors contributing to hyperuricemia in most patients with gout. Some of these factors, such as obesity, a high-purine diet, regular alcohol consumption, and diuretic therapy, may be correctable. In patients with persistent hyperuricemia, regular medication should lower the serum urate concentration to an optimal level. The continuing challenge is to educate patients about correctable factors and the importance of regular medication and ensure their compliance so that attacks of gout do not recur.

Urinary excretion of vitamin B12, folic acid, and citrovorum factor in human subjects on various diets.

The average urinary excretion of vit. B12 in 14 subjects on normal diets was found to be 31 my per day. Similar values were obtained in 28 subjects maintained for 3 days on the following diets: milk, alkaline ash? low protein, and high protein. A somewhat higher value was found in 8 subjects on high purine diets, and the increase over normal was shown to be due to interfering compounds. On the third day of fasting, 6 subjects were found to excrete an average of 62 my vit. B12 per day.