One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.

AIMS: Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis. MATERIALS AND METHODS: Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on. RESULTS: The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on. CONCLUSIONS: Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia.

The effect of anti-Anisakis simplex antibody levels on C3 and C4 complement components in human sera.

Previously, an in vitro effect was observed on the complement system not only of the excretory-secretory products but also of somatic antigens from L3 Anisakis simplex larvae. In the present work the effect of anti-A. simplex specific antibodies on C3 and C4 levels in human sera was investigated. Up to 309 samples of sera were tested to determine levels of C3 and C4 and anti-A. simplex antibodies, including immunoglobulins IgG, IgM, IgA and IgE. Significant differences were observed between levels of C3 and C4 and all immunoglobulins except for IgE. In the case of immunoglobulins, the probability that an anti-A. simplex positive subject has a C3 deficiency was 3.8 times higher than a subject without specific antibodies. In conclusion, an association between elevated levels of anti-A. simplex antibodies and C3 and C4 deficiency was demonstrated.

Differential effect of appendectomy and tonsillectomy on anti-Kudoa sp. antibodies in patients with MALTectomy.

We found an association between tonsillectomized patients and subsequent appendicitis. We also observed that MALTectomy significantly decreased secretory IgA levels in serum of patients, being this decrease more pronounced when both operations (tonsillectomy and appendectomy) had been performed. The elevated humoral responses detected previously by us in BALB/c mice immunized with Kudoa sp. pseudocyst extracts and the high IgG1 and IgE levels induced by the oral administration of Kudoa sp. pseudocysts to BALB/c mice showed the possible immunopathological effects in man from the ingestion of Kudoa sp. infected fish. We use the ELISA method to investigate the possible relationship between MALTectomy (tonsillectomy and appendectomy) and specific antibody levels to Kudoa sp. Both anti-Kudoa sp. specific antibody levels and the number of patients that recognized Kudoa sp. antigens were greater in tonsillectomy patients when compared to the control and the other studied groups (appendectomized and appendectomized+tonsillectomies patients). Tonsillectomy was associated to a switch in the class of immunoglobulins involved in these responses and these responses may be abrogated by appendectomy. Tonsils and appendix may respond in different ways to Kudoa sp. antigens and these different reactions may be involved in some immunopathological reactions.

Seroprevalence of anti-Gymnorhynchus gigas (Trypanorhyncha, Gymnorhynchidae) antibodies in a Spanish population.

The somatic products released from ingested larvae of Gymnorhynchus gigas parasitizing fish induce a Th2 response capable of causing allergic disorders. The objective of the present work was to evaluate the prevalence of anti-Gymnorhynchus gigas antibodies in a Spanish population and established a possible relationship with fish consumption habits. We studied 305 residents in Madrid, with neither clinical symptoms suggestive of gastrointestinal or allergic disorders, nor pathologies related to ingestion of fish that could cause disease. Specific antibody levels were measured by ELISA: 11.8%, 20%, 15.7%, 21%, and 7.5% of the total studied sera were IgA, Ig's, IgG, IgM, and IgE positive, respectively. Seropositivity was not more prevalent among fresh fish consumers and did not increase with frequency of fish consumption. IgE values were lower in the group that never ingested smoked fish. Anti-G. gigas antibody levels were higher in the group that reported frequent consumption of marinated fish. The use of cooking methods with the least heating efficacy (frying, or frying in batter, and microwaving) did not affect seropositivity percentages among consumers. Infection with live plerocercoids is not necessary for seropositivity, and the antibody production, in this case, is due to the absorption of antigens from the parasite following the digestion process. The human health risks of allergic reactions due to parasite antigens remain active after freezing the fish.

Study of the effect of Anisakis simplex larval products on the early and late components in the classical complement pathway.

In previous studies, we have reported that the larval products (crude extract [CE] and excretory-secretory [ES]) of Anisakis simplex showed a dose-dependent inhibition of the lysis mediated by classical (CP) and alternative pathways (AP) of the human complement system, with the major inhibition on the CP rather than on AP. This inhibition of hemolysis is due to the consumption of complement factors because the assays performed shortening the preincubation period result in a significant decrease of the inhibitory effect on the lysis of the larval products compared with the standard time. Likewise, we found that the larval products reduce the inhibitory percentages in the CP using C3-deficient sera, but not in the AP, which could indicate that other complement components are implicated in the inhibitory effect in the CP. Hence, we have studied the activity of the larval products of A. simplex on individual components in the CP, using different complement-deficient sera. The investigated complement molecules were C1q, C2, C4, C5, C6, C7, C8, and C9. The larval products showed activity at the C2 level but failed to have a significant effect on the other components. Therefore, CE and ES products from A. simplex interact with C3 and C2 complement proteins, which are early components of the complement system, but not with the late complement components.

Anisakis simplex: the activity of larval products on the complement system.

The effects of the larval products (crude extract and excretory-secretory) of Anisakis simplex on the classical and alternative pathways of human complement system were investigated. This could constitute a mechanism to evade host defences, similarly than in other parasitic diseases. The larval products showed a stronger effect on the classical pathway than on the alternative pathway. The most pronounced modulating effects were found for the excretory-secretory products. Chelation of bivalent cations (Ca(2+) or Mg(2+)) by these larval products may be responsible for their mode of action on the alternative pathway, whereas the chelation is not likely to be particularly involved in the anticomplementary activity found on the classical pathway. Detailed studies revealed that the larval products of A. simplex act at the level of the C3 and other complement components. Heating the crude parasite extract led to a notable loss of haemolysis inhibition activity, and the addition of PMSF (a serine protease inhibitor) also cause variation in the activity of the crude extract.

Tricobezoar. Una causa rara de dolor abdominal con apariencia radiológica típica / Trichobezoar. A rare cause of abdominal pain with typical X-ray appearance

Un bezoar es una masa compuesta por material extraño ingerido, normalmente fibras vegetales o pelos, en el interior del tubo digestivo. Los tricobezoares son raros y aparecen normalmente en individuos con trastornos mentales. Presentamos una paciente de 16 años, con trastornos emocionales, que consulta por dolor abdominal, vómitos de dos días de evolución y masa en cuadrantes abdominales superiores. Se realiza radiografía convencional, ecografía y tomografía computarizada de abdomen que ponen de manifiesto los signos radiológicos típicos de tricobezoar gástrico. Hacemos especial hincapié en la utilidad de la tomografía computarizada en el diagnóstico preoperatorio y en la detección de posibles complicaciones. La paciente fue tratada mediante laparotomía, gastrotomía y extracción del tricobezoar. El postoperatorio discurrió sin complicaciones y actualmente está en tratamiento por psiquiatría

A bezoar is a ball of swallowed foreign material that is usually vegetable fibers or hairs, in the digestive tract. Trichobezoars are rare and normally appear in individuals with mental disorders. We present the case of a 16 year old woman with emotional disorders who consulted due to abdominal pain, two-day long vomiting and mass in upper abdominal quadrant. A plain X-ray, ultrasonography and CT scan of the abdomen were performed. They showed typical X-ray signs of gastric trichobezoar. We emphasize the utility of the CT scan in the preoperative diagnosis and in the detection of possible complications. The patient was treated by laparatomy, gastrotomy and extraction of the trichobezoar. Post-operative period was without complications and she is currently receiving psychiatric treatment

Limited risk of kidney stone formation during long-term calcium citrate supplementation in nonstone forming subjects.

The physiological and physicochemical effects of long-term calcium citrate supplementation (25 mmol. calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 +/- 0.42 mmol. per day (standard deviation) before treatment to 5.16 +/- 0.75 mmol. per day after 1-month of treatment (p < 0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 +/- 0.67 mmol. per day (p < 0.0125) but remained higher than the pretreatment value (p < 0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 +/- 0.092 to 0.374 +/- 0.035 (p < 0.05) and from 103 +/- 7 to 77 +/- 14 pmol./l. (p < 0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 +/- 0.061 (p < 0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 +/- 14 pmol./l. Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 +/- 3.3 to 15.0 +/- 2.5 mmol. per day (p < 0.0125) and 14.0 +/- 2.5 mmol. per day (p < 0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment. In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.

[Epilepsy and thyrotoxicosis in a 4-year-old boy]. / Epilepsia y tirotoxicosis en un niño de cuatro años.

Hyperthyroidism in childhood has a relative incidence of 5%. The presence of epilepsy secondary to thyrotoxicosis is very unusual. We report the case of a four-year old boy with thyrotoxicosis due to Graves' disease. This patient developed a generalized tonic-clonic seizure followed by left sided partial motor status epilepticus. The EEG was markedly abnormal. The EEG was normal after five months of the ablative therapy. At the present time the patient is seizure-free without any antiepileptic medication and receiving replacement therapy with thyroxin due to post-ablation hypothyroidism. We conclude that this is the first reported case with this association in our country. We discuss the possible pathophysiological mechanism involved in the development of seizures in this patient.