Plant-based chimeric HPV-virus-like particles bearing amyloid-ß epitopes elicit antibodies able to recognize amyloid plaques in APP-tg mouse and Alzheimer's disease brains.

The main amyloid-beta (Aß) variants detected in the human brain are full-length Aß1-40 and Aß1-42 peptides; however, a significant proportion of AD brain Aß consists also of N-terminal truncated/modified species. The majority of the previous immunotherapeutic strategies targeted the N-terminal immunodominant epitope of the full-length Aß; however, most of the pathological N-truncated forms of Aß lack this critical B cell epitope. Recently, virus-like particles (VLPs), self-assembled structures with highly ordered repetitive patterns on their surface and capable of inducing robust immune responses, were applied as a promising platform for various antigen expressions. In this study, we expressed in plants two chimeric HPV16 L1 capsid proteins obtained by introduction of the ß-amyloid 11-28 epitope (Aß 11-28) into the h4 helix or into the coil regions of the L1 protein. The Aß 11-28 epitope was chosen because it is present in the full-length Aß 1-42 as well as in the truncated/modified amyloid peptide species. After expression, we assembled the chimerical L1/Aß 11-28 into a VLP in which the Aß 11-28 epitope is exposed at very high density (360 times) on the surface of the VLP. The chimeric VLPs elicited in mice Aß-specific antibodies binding to ß-amyloid plaques in APP-tg mouse and AD brains. Our study is the first to demonstrate a successful production in plants and immunogenic properties in mice of chimeric HPV16 L1 VLPs bearing Aß epitope that may be of potential relevance for the development of multivalent vaccines for a multifactorial disease such as AD.

Multimodality evaluation of patients with gastroesophageal reflux disease symptoms who have failed empiric proton pump inhibitor therapy.

Patients with symptoms suggestive of gastroesophageal reflux disease (GERD), such as chest pain, heartburn, regurgitation, and dysphagia, are typically treated initially with a course of proton pump inhibitors (PPIs). The evaluation of patients who have either not responded at all or partially and inadequately responded to such therapy requires a more detailed history and may involve an endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory esophageal pH monitoring, and gastric emptying scanning. To assess the merits of a multimodality 'structural' and 'functional' assessment of the esophagus in patients who have inadequately controlled GERD symptoms despite using empiric PPI, a retrospective cohort study of patients without any response or with poor symptomatic control to empiric PPI (>2 months duration) who were referred to an Esophageal Studies Unit was conducted. Patients were studied using symptom questionnaires, endoscopy (+ or - for erosive disease, or Barrett's metaplasia) and multilevel esophageal biopsies (eosinophilia, metaplasia), esophageal motility (aperistalsis, dysmotility), 24-hour ambulatory esophageal pH monitoring (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10% retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men and 128 women) aged 16-89 years underwent complete multimodality testing. Forty percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]-, biopsy-, pH+); 19.3% (n= 53) had erosive esophagitis (EGD+); 5.5% (n= 15) Barrett's esophagus (EGD+, metaplasia+); 5.5% (n= 15) eosinophilic esophagitis (biopsy+); 2.5% (n= 7) had achalasia and 5.8% (n= 16) other dysmotility (motility+, pH-); 16% (n= 44) had functional heartburn (EGD-, pH-), and 5.8% (n= 16) had gastroparesis (gastric scan+). Cumulative symptom scores for chest pain, heartburn, regurgitation, and dysphagia were similar among the groups (mean range 1.1-1.35 on a 0-3 scale). Multimodality evaluation changed the diagnosis of GERD in 34.5% of cases and led to or guided alternative therapies in 42%. Overlap diagnoses were frequent: 10/15 (67%) of patients with eosinophilic esophagitis, 12/16 (75%) of patients with gastroparesis, and 11/23 (48%) of patients with achalasia or dysmotility had concomitant pathologic acid reflux by pH studies. Patients with persistent GERD symptoms despite empiric PPI therapy benefit from multimodality evaluation that may change the diagnosis and guide therapy in more than one third of such cases. Because symptoms are not specific and overlap diagnoses are frequent and multifaceted, objective evidence-driven therapies should be considered in such patients.

Synthesis and Characterization of TiO2 Thick Films for Glucose Sensing.

In this paper, we present the results of a non-enzymatic electrochemical glucose biosensor based on TiO2. An anatase working electrode was synthesized using the spin coating technique with the polymeric precursor method and dispersed TiO2 nanoparticles. Through scanning electron microscopy, it was observed that the electrode presented an irregular surface with clusters of nanoparticles. Electrochemical characterization indicated that the response was directly related to the morphology of the electrode. In the presence of glucose, the electrode exhibited adsorption behavior toward the molecules, enabling their recognition. The electrode was tested by employing PBS (phosphate buffer solutions) with varying pH values (from 4 to 9), demonstrating its electrochemical stability, even in the presence of glucose. Amperometric characterization was used to determine that the working region appeared from 0.2 mM to 2 mM, with a sensitivity of 4.46 µAcm-2mM-1 in PBS pH 7. The obtained results suggest that TiO2-based electrodes could be used for the detection of glucose concentration in sweat (0.277-1 mM) and saliva (0.23-1.77 mM).

[Improvement of fecal incontinence with silicone implants in patients with internal anal sphincter injury: First report in North America]. / Mejoría de la incontinencia fecal con implantes de silicón en pacientes con lesiones del esfínter anal interno: primer informe en Norteamérica.

The injection of bulking agents has been described as a useful treatment of urinary and fecal incontinence. Among them, silicone implants have shown benefits in patients with internal anal sphincter (IAS) injury. We describe two patients with a history of hemorrhoidectomy and IAS injuries, which underwent placement of silicone implants. The implants were inserted into the intersphincteric space and the IAS under ultrasound guidance. The Wexner continente score fell from 17 and 19 before treatment, to 6 and 8 at six months follow up, respectively. Patients had no postoperative complications or implants migration. In our patients, injection of silicone implants improved fecal continence score, without postoperative complications or implants migration at six month follow up.

Preoperative progressive pneumoperitoneum: The answer for treating giant inguinal hernias while avoiding morbidities?

PURPOSE: Preoperative progressive pneumoperitoneum (PPP) is mostly used for giant abdominal incisional hernias, and only a few isolated or paired cases that used PPP in the treatment of giant inguinal hernias (GIH) have been reported. The main objective of this study is to describe our technique in the use of PPP in the treatment of GIH in a series of patients who presented with this challenging condition. METHODS: We retrospectively reviewed the medical records of a series of patients treated with PPP for GIH during a 6-year period (2012-2018) at a single institution. The demographics, preoperative, and surgical characteristics were analyzed. RESULTS: In total, 7 patients were treated for GIH with PPP. The median age was 64 (range 30-89) years. The median history time with the inguinal hernia was 8 (range 2-20) years. The median time of PPP was 22 (range 15-30) days. All patients underwent the Lichtenstein technique. The median follow-up time was 12 (range 3-84) months. Three (42.8%) of the patients had preoperative complications. Two patients developed mild dyspnea during PPP, and another patient had subcutaneous emphysema during the insertion of the catheter. Two (28.5%) patients had postoperative complications. One of them developed a right scrotal abscess, and another patient developed bilateral grade III hydrocele. CONCLUSION: With our limited experience, it is too early to tell if this should be the gold standard for the treatment of GIH. To see if there is superiority among different procedures, more studies that compare the morbidity of PPP with that of other trans operative techniques are needed. Nevertheless, the procedure we propose has provided satisfactory results.

[First case of sacral neuromodulation for treatment of urinary and fecal incontinence in Mexico. Case report.]. / Primer caso de neuromodulación sacrapara el tratamiento de la incontinenciaurinaria y fecal en México. Informe de caso.

Sacral neuromodulation is a new treatment for urinary and fecal incontinence that has demonstrated good therapeutic results. This treatment modality has shown not only to reduce urinary dysfunction symptoms and urinary and fecal incontinence but improve quality of life scores as well. We present a 73 years old female patient with severe fecal and urinary incontinence with major quality of life impact. She was referred after failure of different surgical and conservative therapeutic approaches. Her evaluation met inclusion criteria for sacral neuromodulation treatment. Acute sacral nerve evaluation (PNE) proved to be therapeutic in the patient as measured by at least a 50 percent improvement in her symptoms so a permanent implant (Medtronic InterStim System) was placed. After the implant there was a significant improvement in urinary and fecal functional scores. Fecal Incontinence Severity Index improved from 34 to 8 and Urinary Sandvik's Severity Index from very severe urinary incontinence to minor urinary incontinence after the placement of the implant. Using standard quality of life questionnaires, she improved in the areas of lifestyle,coping and behavior and her experience with depression and self-perception.

Large inguinal bladder hernias: can a preoperative diagnosis be made?

PURPOSE: Bladder hernias are asymptomatic in most cases and are found incidentally during exploration for inguinal hernia repair. The treatment of inguinal bladder hernia is either reduction or resection of the herniated bladder, followed by herniorrhaphy. We present a case series with preoperative diagnoses, along with their surgical outcomes. METHODS: We retrospectively reviewed the medical records from a single institution over a 5-year period (2012-2017) of five patients with diagnosis of large bladder inguinal hernia. Demographics, clinical status, medical history, anatomical structure of the hernia, and surgical outcomes were all analyzed. RESULTS: Patients' median age was 51 years (range 45-81 years). The median size of the hernial sac was 13 cm (range 8-20 cm). The diagnosis was made with computed tomography in three patients and with ultrasonography and cystography in two patients. Median length of hospital stay was 2 days (range 1-6 days), and median length of follow-up was 28 months (range 18-72 months). All patients continue to be alive and well, without hernia recurrence. The five cases are described separately along with their surgical managements. CONCLUSION: The main objectives in treatment of inguinal bladder hernia are to preserve the voiding function and to avoid bladder injuries in a tension-free hernia repair. To our knowledge, this is the first series of cases in which all inguinal bladder hernias were diagnosed preoperatively.

Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist.

SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases.

Medicina de Familia, una especialidad amenazada / Family Medicine, a threatened specialty

No disponible

Efficacy of SR 47436 (BMS-186295), a non-peptide angiotensin AT1 receptor antagonist in hypertensive rat models.

The efficacy of SR 47436 (BMS-186295), 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)- biphenyl-4-yl)methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one, a non-peptide angiotensin AT1 receptor antagonist, was characterized in various conscious hypertensive rat models. In spontaneously hypertensive rats, single intravenous or oral doses of SR 47436 induced mild to modest antihypertensive effects. No tolerance of the antihypertensive effect was observed when the oral treatment was extended to 15 days. SR 47436 was highly effective to lower blood pressure in high renin-dependent hypertensive models such as two-kidney, one-clip renal hypertensive rats and renal artery-ligated hypertensive rats. In this last model, intravenous or oral administration of the angiotensin II antagonist produced a dose-dependent decrease in blood pressure. When injected after the maximal effective dose, enalapril did not induce any further decrease in blood pressure. Furthermore, the antihypertensive effect elicited after a single oral dose (10 mg/kg) was long-lasting (at least 24 h). The simultaneous blunting effect of the angiotensin II-induced blood pressure increase indicated clearly that the antihypertensive effect was due to the blockade of vascular angiotensin AT1 receptors. As expected, the angiotensin AT1 receptor antagonist did not show any efficacy in deoxycorticosterone acetate hypertensive rats, with a suppressed renin-angiotensin system. In genetic and renal hypertensive rats, the antihypertensive effect induced after acute dosing of SR 47436 was similar to that observed after losartan and enalapril. A reflex tachycardia accompanied the antihypertensive effect only after intravenous treatment with either SR 47436 or losartan. These results show that this angiotensin II antagonist, SR 47436, is an effective and long-lasting antihypertensive agent in rats.

Aquaretic and hormonal effects of a vasopressin V(2) receptor antagonist after acute and long-term treatment in rats.

A single oral administration of 1-[4-(N-tert-butylcarbamoyl)-2-methoxybenzene sulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethoxy)cyclohexane]indo l-2 -one SR121463 (0.3-3 mg/kg), a vasopressin non-peptide V(2) receptor antagonist, to rats induced dose-dependent aquaresis which was accompanied by Na(+), K(+), aldosterone and arginine vasopressin excretion over 6 h after dosing. However, no solute excretion was observed over 24 h. As a result of aquaresis, hemoconcentration and increases in plasma angiotensin II and adenocorticotrophin hormone were seen with 3 mg/kg at 2 h after dosing. Chronic treatment with SR121463 (3 mg/kg/dayx28 days) induced a marked aquaresis associated with aldosterone and vasopressin excretion. After a week of treatment, urine volume and aldosterone excretion were reduced ( approximately 40%) and then stabilised, while urine vasopressin excretion remained almost constant throughout the study. There were no changes in arterial pressure, plasma osmolality, plasma sodium concentration, or in number and affinity of liver vasopressin V(1A) and kidney V(2) receptors 24 h after the last treatment. These results indicate that SR121463 is a potent aquaretic agent and might be useful for the chronic management of water-retaining diseases in humans.

Some limiting factors of the ion-exchange equilibrium method for determining apparent formation constants of mononuclear complexes.

Some limiting analytical conditions of the ion-exchange equilibrium method are discussed. The most reliable apparent formation constants are obtained when the range of the experimental complexant concentration brackets the reciprocal value of the stability constant for ML-type complexes. This working range will ensure significant analytical differences in the total metal remaining in solution for successive experiments with increasing complexant concentrations. For accurate determination of stepwise formation constants for ML(2)-type complexes, the intermediate complex species ML(+) must not be exchanged by the resin to any extent. Otherwise Schubert's equations are no longer valid, and the partition ratios of all cationic species present should be taken into account.

[Hypotensive effect of a new calcium antagonist, SR 33557 in conscious rats]. / Effet hypotenseur d'un nouvel antagoniste calcique, le SR 33557, chez le rat vigile.

SR 33557 (SR) is a new calcium channel blocker belonging to the chemical class of indolizinsulfones (IC50 = 0.6 nM, 3H-nitrendipine). Its hypotensive effects were studied in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and compared to those of Nitrendipine (Nit) (IC50 = 0.8 nM, 3H-nitrendipine). SR was given intravenously (IV) at 0.3, 1 and 3 mg/kg (n = 4 to 6) and orally (PO) at 3, 10, 30 and 60 mg/kg (n = 4 to 7). Nitrendipine was studied at 0.3 mg/kg (IV) and 10 mg/kg (PO). Blood pressure (BP) and heart rate (HR) were measured for 120 min, and for 24 h at 30 mg/kg. The IV injection of SR induced an immediate and dose-dependent decrease in BP. The maximal diastolic hypotension was situated between 11 p. 100 at 0.3 mg/kg and 45 p. 100 at 3 mg/kg (basal values: 133 +/- 6 and 131 +/- 5 mmHg). These effects lasted between 30 min and over 2 hours. The oral administration of SR induced a dose-dependent fall in BP at 3 mg/kg and upwards. The maximal diastolic hypotension appeared within 60 and 120 min and were situated between 8 p. 100 at 3 mg/kg and 28 p. 100 at 60 mg/kg (basal values: 130 +/- 7 and 133 +/- 2 mmHg). At 30 mg/kg, the hypotension lasted for 8 hours. SR was roughly 10 times less hypotensive in WKY than in SHR. HR did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute hepatitis caused by Listeria monocytogenes infection]. / Hépatite aiguë due à une infection par Listeria monocytogenes.

We report the case of a 40 year-old woman, pregnant for 4 months, with acute hepatitis revealed by jaundice, fever and high serum aminotransferase levels. Infection by Listeria monocytogenes was demonstrated by blood cultures. The course of the disease was characterized by abortion and complete recovery of hepatitis within 4 weeks after antibiotic administration. This report shows that listeriosis can cause acute severe hepatitis.

[Zoonotic brucellosis risk associated with clandestine slaughtered porks]. / Risco de brucelose zoonótica associado a suínos de abate clandestino.

To determine the sanitary risk to human health, 59 sera samples of clandestine slaughtered porks were examined through serologic procedures and have demonstrated to have anti-Brucella antibodies and antibodies titles suggestive of brucellosis infection. Surveillance measurements are recommended to prevent potential risk of zoonotic infection.

[Fistulotomy vs fistulectomy. Ultrasonographic evaluation of lesion of the anal sphincter function]. / Fistulotomía vs fistulectomía. Valoración ultrasonográfica de lesión al mecanismo de esfínter anal.

OBJECTIVE: To determine the extension of the lesion implicated on the mechanism of the anal sphincter with endoanal ultrasound in patients with simple fistulae, managed with fistulotomy versus fistulectomy. SITE: Central Military Hospital. Colon and Rectum Service. DESIGN OF STUDY: A prospective, comparative, descriptive and longitudinal study was performed. METHODS: A total of 40 patients with anal simple fistula were studied from march 1997 to march 1998. They were divided in two randomized groups: group A (n = 20) patients treated with fistulectomy, and group B (n = 20) patients managed with fistulotomy. Endoanal ultrasound was practice at the time of the diagnosis and six weeks later to identify integrity of both internal and external anal sphincter, and to register them in separate form. RESULTS: There were no significant differences in sex and age distribution, nor in type of fistula. The average of internal anal sphincter lesion in inter-sphincteric fistulae treated with fistulotomy was 8.5 mm versus 9.08 with fistulectomy (p > 0.05). The average of internal and external anal sphincter lesion in trans-sphincteric fistulae managed with fistulotomy was 9.25 mm versus 11.38 with fistulectomy (p < 0.05). The global analysis showed that the average of the lesion in the sphincter, mechanism was larger in the fistulectomy versus fistulotomy (p < 0.05). CONCLUSION: The major muscular injury made to the sphincter mechanism is caused mainly by the fistulectomy in comparison with the conventional fistulotomy.