O objetivo com o presente trabalho foi avaliar o efeito do preparado de anticorpos policlonais (PAP) contra bactérias ruminais específicas (Streptococcus bovis e Fusobacterium necrophorum) sobre o consumo de matéria seca, digestibilidade aparente total da dieta, parâmetros de fermentação ruminal e contagem ruminal de protozoários, em animais adaptados ou não a dietas com alta proporção de carboidratos fermentescíveis. Foram utilizadas 6 vacas fistuladas no rúmen em dois quadrados latinos 3x3, em arranjo fatorial de tratamentos 3x2 referentes a dois aditivos PAP pó (PAPP) e PAP líquido (PAPP), mais o grupo controle e 2 tipos de manejo de adaptação à dieta. O primeiro quadrado latino recebeu uma adaptação gradual à dieta: do D0 ao D4 100% forragem; D5 ao D9 30% de concentrado e do D10 ao D14 60% de concentrado. O segundo quadrado latino recebeu 100% de forragem do D0 ao D14. Nos dias D15 e D16, todos os animais receberam uma dieta com 80% de concentrado. Para as análises, amostras de líquido ruminal foram coletadas diariamente às 3 h após a alimentação matinal. Os dados foram analisados pelo procedimento MIXED do SAS com nível de significância de 0,05. A variável consumo de matéria seca apresentou efeito de interação entre tempo e adaptação à dieta com alta proporção de carboidratos prontamente fermentescíveis (P<0,0001), onde o grupo adaptado apresentou consumo mais elevado em relação aos não adaptados (12,4 vs 6,6, respectivamente) do D0 ao D17. Para a variável digestibilidade da MS foi observado efeito de adaptação (P<0,0001), sendo que nos animais adaptados, a digestibilidade da MS foi superior (65,9%) à dos não adaptados (55,3%). Foi também observado efeito de aditivo (P=0,0186), onde o tratamento com PAPL apresentou maior digestibilidade da MS (63,6%), quando comparados aos tratamentos PAPP e controle (58,4% e 59,6%, respectivamente). A digestibilidade da PB apresentou efeito de interação entre proporção de carboidratos na dieta e o tipo de adaptação (P<0,0001), onde os animais adaptados apresentaram maior digestibilidade da PB (83,2%) em comparação aos não adaptados (79,3%), ambos recebendo 100% de forragem. Quando os animais adaptados receberam 60% de concentrado na dieta, este grupo apresentou menor digestibilidade da PB (69,4%), quando comparado ao grupo de animais não adaptados (83,6%). Já para a variável digestibilidade da FDN, os animais adaptados apresentaram maior digestibilidade da FDN (40,6%) em relação aos não adaptados (36,3%) (P=0,0332). Quanto ao efeito de aditivo (P=0,0248), os animais tratados com o aditivo PAPL apresentaram maior digestibilidade da FDN (44,0%), quando comparados aos tratados com PAPP (36,2%) e o grupo controle (35,4%). Quanto à digestibilidade do amido, foi observada interação entre dieta e adaptação (P=0,05), onde, na segunda semana, o grupo dos adaptados apresentou maior digestibilidade (92,8%) quando comparado ao grupo dos não adaptados (73,9%). Para a digestibilidade de carboidratos totais, foi observado efeito de adaptação (P<0,0001) e de aditivo (P=0,0312), onde o grupo dos adaptados apresentou maior digestibilidade quando comparados aos não adaptados (66,4% vs. 55,5, respectivamente), e os animais tratados com PAPL, apresentaram maior digestibilidade (63,9%) de carboidratos totais, que os tratados com PAPP (59,0%) e controle (59,9%). Ocorreu interação entre tempo e adaptação para a variável pH (P <0,0001), sendo que o grupo adaptado apresentou menor pH (6,40) quando comparado ao grupo dos não adaptados (6,77) entre o D2 e o D16. Ainda, foi verificado efeito de aditivo sobre a variavel pH ruminal (P=0,0432), onde o grupo PAPL apresentou maiores valores (6,62) quando comparado ao grupo PAPP (6,57) e ao controle (6,56). Ocorreu interação entre tempo e adaptação (P<0,0001) para a concentração AGCCt, onde os animais adaptados apresentaram valores mais elevados que o grupo dos não adaptados (100,3 vs. 77,7, respectivamente). Para a variável relação acetato:propionato (Ac:Pr), houve efeito de interação entre tempo e adaptação (P<0,0001). No D2, 5, 6 e D7, o grupo dos animais adaptados apresentou menor relação Ac:Pr quando comparados aos animais não adaptados (2,29 vs. 1,96, respectivamente). Porém, nos dias 12 a 16, houve inversão desta relação e os animais adaptados passaram a apresentar maior relação Ac:Pr (2,87) quando comparados ao grupo dos não adaptados (2,41). Não foi observado efeito de adaptação (P>0,05) bem como aditivo (P>0,05) para a variável concentração de lactato no líquido ruminal. A concentração de N-NH3 apresentou interação entre tempo e adaptação (P=0,0003), onde o grupo dos adaptados apresentou maiores valores quando comparado ao dos não adaptados (24,68 vs 15,97 mg/dL, respectivamente) entre o D1 e D15. Quanto as populações de protozoários, observou-se interação entre tempo, adaptação e aditivo para as populações de Dasytricha sp (P=0,0305) e Entodinium sp (P=0,0398), sendo observada manutenção das populações de Dasytricha sp (P=0,0188) nos animais não adaptados e decréscimo nos animais adaptados. Conseqüentemente, para a população de Entodinium sp, foi observado aumento nos animais adaptados (80,78%) e manutenção nos não adaptados (45,3%). Nos animais tratados com PAPL, a população de Dasytricha sp foi superior (38,3%) quando comparados às populações dos tratados com PAPP (31,50%) e grupo controle (34,7%), sem diferença entre estes últimos dois grupos. Quanto a população de Entodinium sp, os animais tratados com PAPL apresentaram menor porcentagem deste gênero de protozoários (58,5%) quando comparados ao grupo controle (64,0%) e ao PAPP (66,7%). A partir dos resultados obtidos foi possível concluir que o preparado de anticorpos policlonais tanto na apresentação líquida como em pó não alterou o consumo de matéria seca bem como a concentração AGCCt, proporção molar de acetato, propionato e butirato, assim como a concentração ruminal de lactato e N-NH3. O preparado de anticorpos policlonais na apresentação líquida melhorou a digestibilidade da MS, FDN e carboidratos totais. Quanto ao pH ruminal, o PAP na apresentação líquida, se mostrou mais eficiente, em evitar a sua redução, quando comparado ao preparado na apresentação em pó e que o grupo controle durante o pico de fermentação. A adaptação melhorou a digestibilidade da MS, PB, EE, FDN, FDA e carboidratos totais, assim como aumentou as concentrações de AGCCt, sem que ocorresse aumento nas concentrações de lactato. / The objective with the present work was to evaluate the polyclonal antibody preparation (PAP) against specific rumen bacteria (Streptococcus bovis and Fusobacterium necrophorum) on dry matter intake, total apparent digestibility of diet, ruminal fermentation patterns and ruminal protozoa counting on adapted and non-adapted animals to highly fermentable carbohydrates diets. Six ruminally cannulated cows were used in two Latin squares 3x3, in a factorial arrangement of treatments 3x2 regarding two feed additives (PAP in powder presentation (PAPP) and PAP in liquid presentation (PAPL)) plus control group (CON) and two managements of diets adaptation. The first Latin square received a step-up diet adaptation: from D0 to D4 100% forage; D5 to D9 30% of concentrates and D10 to D14 60% of concentrates. The second Latin square received 100% forage from D0 to D14. On D15 and D16, all animals received a diet with 80% of concentrates. For analysis, rumen fluid samples were daily collected 3h after morning meal. Data were analyzed by MIXED procedure with a significance level of 0.05. The variable dry matter intake presented interaction between time and adaptation to highly fermentable carbohydrate diets (P<0.0001), where the adapted group had greater DMI compared with non-adapted animals (12.4 vs. 6.6, respectively) from D0 to D17. For DM digestibility, it was observed effect of adaptation (P<0.0001), where the adapted group had greater values (65.9%) compared with the non-adapted group (55.3%). It was also observed effect of additive for this variable (P=0.0186), where the treatment PAPL had greater DM digestibility (63.6%) compared with treatments PAPP and control (58.4% and 59.6%, respectively). Crude protein digestibility had effect of interaction between carbohydrate proportion in diet and type of adaptation (P<0.0001), where the adapted animals had greater CP digestibility (83.2%) in relation to non-adapted animals (79.3%), both receiving 100% of forage. When the adapted animals received 60% of concentrates in diet, this group had lower CP digestibility (69.3%) compared with non adapted group (83.6%). For NDF digestibility, adapted animals had greater values (40.6%) in relation to non-adapted animals (36.3%) (P=0.0332). It was also observed an additive effect (P=0.0248), where the animals in PAPL group had greater NDF digestibility (44.0%) compared with PAPP (36.2%) and control (35.4%) groups. For starch digestibility, it was observed interaction between diet and adaptation (P=0.05), where, in the second week, the adapted group had greater digestibility (92.8%) compared with non-adapted group (73.9%). For total carbohydrates digestibility, it was observed effect of adaptation (P<0.0001) and additive (P=0.0312), where the adapted group had greater values compared with non-adapted animals (66.4% vs. 55.5, respectively), and the animals in PAPL group had greater total carbohydrates digestibility (63.9%) than PAPP (59.0%) and control (59.9%) groups. It was observed an interaction between time and adaptation for ruminal pH (P <0.0001), where the adapted group had lower pH (6.40) compared with non-adapted group (6.77) between D2 and D16. Moreover, it was verified additive effect for ruminal pH (P=0.0432), where PAPL group had higher values (6.62) compared with PAPP (6.57) and control (6.56) groups. It was observed an interaction between time and adaptation (P<0.0001) for total concentration of short chain fatty acids (SCFA), where the adapted animals had greater values than non-adapted animals (100.33 vs. 77.72, respectively). For acetate:propionate ratio (Ac:Pr), there was effect of interaction between time and adaptation (P<0.0001). At D2, 5, 6 and D7, the group of adapted animals had lower Ac:Pr ratio than non-adapted group (2,29 vs. 1,96, respectively). However, at D12 to D16, there was an inversion of this relation and the adapted animals had greater Ac:Pr ratio (2.87) when compared with non-adapted animals (2.41). It was not observed effect of adaptation (P>0.05) as well as effect of additive (P>0.05) for ruminal lactate concentration. The concentration of N-NH3 showed interaction between time and adaptation (P=0.0003), where the adapted group had greater values compared with non-adapted group (24.7 vs. 16.0 mg/dL, respectively) between D1 and D15. For rumen protozoa population, it was observed an interaction between time, adaptation and additive for Dasytricha sp (P=0.0305) and Entodinium sp (P=0.0398), where the number of Dasytricha sp (P=0.0188) population was maintained in non-adapted animals and decreased in adapted animals. Consequently, for Entodinium sp population, it was observed increase in its number in adapted animals (80.8%) and maintenance of its number in non-adapted animals (45.3%). In animals treated with PAPL, the population of Dasytricha sp was greater (38.3%) when compared with the animals treated with PAPP (31.5%) and control group (34.7%), without difference between these last two groups. For Entodinium sp population, the animals treated with PAPL had lower percentage of these protozoa (58.5%) when compared with control (64.0%) and PAPP (66.7%) groups. From these results, it was possible to conclude that polyclonal antibody preparation both in liquid or powder presentation did not alter dry matter intake, total concentration of SCFA, molar proportion of acetate, propionate and butyrate as well as ruminal concentration of lactate and NH3-N. Polyclonal antibody presentation in liquid presentation improved DM, NDF and total carbohydrates digestibility. For ruminal pH, PAP in liquid presentation was more efficient in preventing its reduction, when compared with PAP in powder presentation and control group during the peak of fermentation. Adaptation to highly fermentable carbohydrate diets improved DM, CP, EE, NDF, NDA and total carbohydrates digestibility even as increased total concentration of SCFA without increase in lactate concentration.

O presente estudo objetivou avaliar o efeito do balanço cátion-aniônico da dieta sobre: (a) concentração de subunidades de caseína, proteínas do soro, cálcio iônico e estabilidade do leite ao etanol e ao aquecimento a 140&ordm; C; (b) metabolismo digestivo, renal e sanguíneo de vacas leiteiras em lactação. Foram utilizadas 16 vacas da raça Holandês, com 158 &plusmn; 52 dias em lactação, distribuídas em 4 quadrados contemporâneos em um delineamento Quadrado Latino 4 x 4, com 4 períodos de 21 dias e 4 tratamentos. Os tratamentos experimentais consistiram de 4 níveis de balanço cátion-aniônico da dieta (BCAD): +290; +192; +98 e -71 mEq/kg de MS. No presente estudo, o consumo de matéria seca, as concentração de ácidos graxos de cadeia curta (AGCC) e o pH do fluído ruminal, e a digestibilidade aparente total da FDN aumentaram de acordo com o aumento do BCAD. De forma semelhante, a produção de leite corrigida para gordura, e os teores de gordura, lactose, e sólidos totais do leite aumentaram linearmente em 13,52, 8,78, 2,5 e 2,6%, respectivamente, quando o BCAD aumentou de -71 para 290 mEq/kg MS; enquanto que os teores de proteína bruta e de caseína reduziram linearmente em 4,83 e 4,49%, respectivamente. Adicionalmente, a concentração sanguínea de HCO3&#x2D; o pH do sangue e a excreção urinária de Na e K aumentaram de acordo com o BCAD, o que reduziu as concentrações sanguíneas de cátions (Na, K e Ca iônico) e, consequentemente, a concentração de Ca iônico do leite. Como resultado da redução da concentração de Ca iônico, a estabilidade do leite ao etanol e ao aquecimento a 140&ordm; C aumentaram linearmente com o BCAD [&#x59; = 74,87 (EP = 0,87) + 0,01174 (EP = 0,0025) × BCAD (mEq/kg MS) e &#x59; = 3,95 (EP = 1,02) + 0,01234 (EP = 0,0032) × BCAD (mEq/kg MS), respectivamente]. Desta forma, pode-se concluir que o BCAD aumenta o desempenho produtivo de vacas leiteiras em lactação e, adicionalmente, eleva a capacidade relativa das proteínas do leite em resistir à coagulação ao teste do álcool e durante o aquecimento do leite a 140&ordm; C. / The present study aimed to evaluate the effect of dietary cation-anion difference (DCAD) on: (a) concentrations of casein subunits, whey proteins, ionic calcium, and milk ethanol and heat stability at 140&ordm; C; (b) digestive, renal and blood metabolism of dairy cows. Sixteen Holstein cows, with 158 &plusmn; 52 days in milk, were distributed in 4 contemporary 4 x 4 Latin Square design, with four periods of 21 days and 4 treatments. The experimental treatments consisted in 4 levels of dietary cation-anion difference (DCAD): +290; +192; +98 e -71 mEq/kg DM. In the present study, dry matter intake, the concentration of short chain fat acids (SCFA) and ruminal pH, and the NDF total apparent digestibility increased according to DCAD increases. Similarly, fat-corrected milk and fat, lactose and total milk solids content were linearly increased by 13.52, 8.78, 2.5 and 2.6%, respectively, according to DCAD increases from -71 to 290 mEq/kg DM; while crude protein and casein content were linearly reduced by 4.83 and 4.49%, respectively. In addition, blood concentration of HCO3&#x2D;, o pH of blood, and urinary excretion of Na and K increased according to DCAD, which reduced the blood concentrations of cations (Na, K and ionic Ca) and, consequently, the milk concentrations of ionic Ca. As a result of reduction of ionic Ca concentration, the milk ethanol and heat stability at 140&ordm; C linearly increased with DCAD [&#x59; = 74.87 (SE = 0.87) + 0.01174 (SE = 0.0025) × DCAD (mEq/kg DM) and &#x59; = 3.95 (SE = 1.02) + 0.01234 (SE = 0.0032) × DCAD (mEq/Kg DM), respectively]. Thus, it may be concluded that DCAD increases the productive performance of lactating dairy cows and, additionally, increases the relative capacity of milk proteins to resist the coagulation at alcohol test and during heat treatment at 140&ordm; C.

A heterogeneidade intratumoral é um fenômeno extremamente importante para entender a progressão tumoral e a resposta à intervenção terapêutica. A galectina-3 pertence à família das lectinas, possuem a função de reconhecimento e ligação à ?-galactosídeos ramificados de glicolipídeos e glicoproteínas, e está envolvida em processos fisiológicos e patológicos como o câncer. Nesse trabalho, a heterogeneidade intratumoral em relação à expressão de galectina-3 foi observada em amostras de diferentes lesões melanocíticas de pacientes. Além disso, o inóculo de células de melanoma murino negativas para galectina-3 em animais gal3-/- gerou tumores constituídos por uma fração de células tumorais que passaram a expressar de novo galectina-3, sugerindo que pressões do microambiente tumoral modulam a expressão dessa lectina em melanomas. A acidose extracelular atuou como regulador negativo de galectina-3 in vitro, diminuindo a expressão dessa lectina tanto em células de melanoma murino e humano quanto em melanócito murino. Entretanto, a hipóxia, seja pela exposição aguda ou intermitente, não alterou a expressão in vitro de galectina-3 em células de melanoma humano. Por fim, tumores originados pelo inóculo de células tumorais positivas e negativas para galectina-3 (mimetizando tumores heterogêneos) obtiveram a maior taxa de crescimento tumoral comparados aos tumores constituídos por uma única população de células, seja positiva ou negativa para galectina-3. Portanto, foram apresentadas evidências de que a heterogeneidade intratumoral em relação à galectina-3 parece estar envolvida com o sucesso evolutivo do melanoma e que a acidose é indicada como uma das pressões microambientais que contribuem para o estabelecimento e manutenção da fração de células tumorais negativas para galectina-3 dentro da massa tumoral / The intratumoral heterogeneity observed in human tumors is extremely important to understand tumor progression and its therapeutic response. Galectin-3 belongs to animal lectin family and it is a ?-galactosidase binding protein which is involved in physiological and pathological processes, including cancer. In this work, an intratumor heterogeneous galectin-3 expression was observed in tissue sessions containing different human melanocytic lesions. Moreover, negative galectin-3 murine cells injected into gal3-/- mice were able to generate tumors composed of a positive galectin-3 cell fraction, suggesting that selective forces in tumor microenvironment modulate galectin-3 expression in melanoma. Extracellular acidosis acts as a negative regulator to galectin-3 in vitro, decreasing its expression in murine and human melanoma cells and even in murine melanocytes. However, intermittent or acute hypoxia exposure did not alter galectin-3 expression in human melanoma cells in vitro. In addition, tumors originated from a mixture of positive and negative galectin-3 cells (mimicking heterogeneous tumors) showed higher growth rate compared to those derived from only galectin-3 positive or negative cells. Therefore, we showed evidences that galectin-3 intratumoral heterogeneity seems to be involved with the evolutionary success of melanoma and that acidosis may be the microenvironmental pressure responsible for the establishment and maintenance of galectin-3 negative cell fraction into the tumor bulk

Mitochondrial disorders are considered to be the most common cause of metabolic abnormalities in the paediatric neurology population (Zeviani et al., 1996). These authors reported that the phenotypes observed in 25-30% of the paediatric patients in their neurology clinics were due to a mitochondrial aetiology. The genetic aetiology in an equivalently affected paediatric population in South Africa is currently unknown. This study investigated the possibility that reported mutations could account for the mitochondrial phenotypes observed in the South African population. It focussed on the most frequent paediatric mitochondrial disorders namely: Leigh Syndrome (LS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and myoclonic epilepsy and ragged red muscle fibres (MERRF). A clinically well characterised group of 25 patients with mitochondrial disorders was included in this study. The molecular analysis of the mitochondrial genome was initially based on a restriction fragment length polymorphism (RFLP) screening strategy for the ten most common mitochondrial DNA (mtDNA) mutations associated with the above¬mentioned three disorders. However, during the study the mutation analysis strategy was modified to a sequencing strategy as this provided more information than the RFLP approach. The modified sequencing strategy extended the study to incorporate fifteen additional mtDNA mutations, associated with other mitochondrial disorders, and individuals included in the study were thus investigated for the presence of 25 mtDNA mutations. Moreover, the modified strategy provided additional information of the regions encompassing the reported mutations. A single patient was observed to harbour the reported A3243G MELAS mutation. This mutation was noted to be heteroplasmic in the proband and two of her maternal relatives. None of the other 24 reported mutations were observed in this patient population. One novel mtDNA alteration in the tRNALeu(UUR) gene was observed in a single patient, although the pathogenicity of this mutation remains to be investigated. Novel and reported polymorph isms, some of which are associated with specific haplogroups, were also observed when comparing sequencing data against the Cambridge reference sequence. The data generated during this study contributed towards the understanding of the uniqueness of the South African population in the global context. This was apparent from the fact that only one of the reported mutations was observed in our patient population who were clinically well characterised and displayed phenotypes similar to those reported internationally. Results form this study underlined the complexity of mitochondrial disorders and argues in favour of whole mitochondrial genome sequence information to be used for diagnostic purposes. Moreover, the results confer with the hypothesis that novel mitochondrial mutations may account for the majority of mitochondrial phenotypes observed in the South African population. / Dissertation (MSc (Human Genetics))--University of Pretoria, 2007. / Genetics / unrestricted

Rumen acidosis is a metabolic disorder of ruminants, characterized by a severe drop in rumen pH. This is due to an accumulation of acids, especially lactic acid in the rumen. Lactic acid is one of the strongest acids with a major effect on rumen pH. A low and / or fluctuating rumen pH can have a severe impact on the productivity and health of dairy cattle, especially during the early lactation period. Rumen acidosis can, for example, occur during the rapid change from a low concentrate to a high concentrate diet. Megasphaera elsdenii (Me) is a lactate-utilizing micro-organism that converts the lactic acid that is produced from the fermentation of starch in the rumen, to propionic acid. Based on the ability of Me to convert lactic acid to propionic acid, a study was conducted to determine the effect of dosing live sources of Me on the level of rumen acidosis, general health and productivity. Sixty high-producing multiparous dairy cows were used in a randomized complete block design experiment. Cows were blocked according to milk production during the previous lactation and, thereafter, randomly allocated, within each block, to one of the following treatments: <ol> <li> 60% concentrate TMR;</li> <li> 60% concentrate TMR with Me dosing;</li> <li> 70% concentrate TMR;</li> <li> 70% concentrate TMR with Me dosing.</li></ol> The experimental period was 60 days and cows were dosed on day 2, 10 and 20 post-partum. Cows were housed in a semi-intensive housing unit equipped with Calan gates for determining individual feed intake. Daily milk production and dry matter intake were measured, as well as body mass and body condition score. Milk was analyzed for fat, protein, lactose and MUN; rumen fluid for pH, volatile fatty acids and lactic acid; faecal samples for pH and starch and feed refusal samples for nutrient components. In addition the health statuses of the cows were also monitored. In general the results did not show a clear advantage of dosing Me, regardless of the level of concentrate. Dry matter intake, milk production, milk composition, feed efficiency, body mass and body condition score were not affected by treatment (P > 0.05). Contrary to expectation, treatment did not affect rumen pH, rumen lactic acid or volatile fatty acid concentrations (P > 0.05). Faecal pH, however, was higher and the starch content lower in cows dosed with Me (P < 0.05) suggesting a positive effect on rumen fermentation and more efficient total tract starch fermentation. Furthermore only two cows were culled from the dosed group, compare to eleven from the control group, suggesting a positive influence of Me on the general health of stress, early lactation cows. Further research is needed to better quantify the potential role of Me in preventing SARA. / Dissertation (MSc(Agric))--University of Pretoria, 2008. / Animal and Wildlife Sciences / unrestricted

Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5-7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.

No description available.

No description available.