ABSTRACT
The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Carotid Body/drug effects , Carotid Body/metabolism , Hyperglycemia/metabolism , Solitary Nucleus/metabolism , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism , Animals , Brain-Derived Neurotrophic Factor/administration & dosage , Enzyme-Linked Immunosorbent Assay , Glucose/metabolism , Hyperglycemia/chemically induced , Hyperglycemia/pathology , Immunohistochemistry , Male , Microinjections , Neurotransmitter Agents/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Random Allocation , Rats, Wistar , Receptor, trkB/agonists , Receptor, trkB/antagonists & inhibitors , Receptor, trkB/metabolism , Receptors, AMPA/agonists , Receptors, AMPA/antagonists & inhibitors , Receptors, AMPA/metabolism , Sodium Cyanide/pharmacology , Solitary Nucleus/cytology , Solitary Nucleus/drug effects , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/administration & dosageABSTRACT
Centruroides tecomanus is a medically important scorpion of the state of Colima (Mexico). This communication reports the identification of venom components of this scorpion with biological activity over insects/crickets (Acheta domestica), crustaceans/fresh water shrimps (Cambarellus montezumae), and mammalians/mice (Mus musculus, strain CD1). It also describes the pharmacological effects on cell lines in culture (L5178Y cells, HeLa cells, HuTu cells and Jurkat E6-1 cells), as well as on several types of bacteria (see below). The soluble venom of this scorpion was fractionated by high-performance liquid chromatography (HPLC) and collected separately in twelve independent fractions collected over 60 min run (5 min time apart each other). The HPLC components of fraction VII were lethal to all three species used for assay. The IVth fraction had a toxic effect on freshwater shrimps. In this species, fractions VI, VII and VIII were all lethal. For crickets, fractions V and VI were toxic and fraction VII was lethal. In mouse, the lethal components were found in fraction VII, whereas fraction VIII was toxic, but not lethal, at the doses assayed. The molecular weight of peptides from the various group of fractions were identified by mass spectrometry determination. Components lethal to mice showed molecular weights from 7013 to 7487 Da. Two peptides were obtained in homogeneous form and shown to be lethal to the three species of animal used for assay. The soluble venom tested on L5178Y cell line survival was shown to be cytotoxic, at 10-100 µg/mL concentration, when compared to control murine splenocytes (p = 0.007). The soluble venom applied to Hela, Hutu and Jurkat cell lines did not show cytotoxic effects at these concentrations. On the contrary, it seems to have a proliferative effect. However the HPLC fractions I, III, VI and XII do have a cytotoxic effect on Jurkat E06-1 cells in culture at 200 µg/mL concentration. The antimicrobial activity of the venom fractions on Staphylococcus aureus (gram-positive), Escherichia coli, Pseudomonas aeruginosa y Salmonella spp (gram-negative) was measured, using the liquid inhibition growth system. The four strains of bacteria used were susceptible to fractions III and IV, affecting all four bacterial strains at concentrations below 5 µg/mL.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Apoptosis/drug effects , Drug Discovery , Insecticides/isolation & purification , Scorpion Venoms/chemistry , Amino Acid Sequence , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Arthropod Proteins/chemistry , Arthropod Proteins/isolation & purification , Arthropod Proteins/pharmacology , Arthropod Proteins/toxicity , Astacoidea/drug effects , Astacoidea/growth & development , Cell Line, Tumor , Cells, Cultured , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gryllidae , Humans , Injections, Intraperitoneal , Insecticides/chemistry , Insecticides/pharmacology , Insecticides/toxicity , Mexico , Mice , Microbial Sensitivity Tests , Scorpion Venoms/administration & dosage , Scorpion Venoms/toxicity , Scorpions/growth & development , Spleen/cytology , Spleen/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & developmentABSTRACT
The aim of this randomized, double-blind clinical trial was to determine the effectiveness of systemic antibiotic application followed by either topical ionized solution (IS) or topical saline solution (placebo) as surgical site infection (SSI) prophylaxis in appendectomy for non-perforated appendicitis. Prophylactic antibiotic was administered pre-incision and either topical IS or placebo was applied pre-suturing to 529 patients, who were then monitored for 30 days. When topical IS was used, SSI relative risk was 0.739 (95% CI 0.537, 1.019) and the SSI prevention rate was 26.06% (CI -1.8%, 46.3%). The number needed to treat was 14.80 patients and the number needed to harm was 209 in order for SSI to be avoided. In conclusion, there was a trend for topical IS prophylaxis to reduce SSI frequency in patients undergoing appendectomy for non-perforated appendicitis, but the result was not statistically significant.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Solutions/administration & dosage , Solutions/therapeutic use , Surgical Wound Infection/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Appendectomy/adverse effects , Appendicitis/surgery , Bacteria/classification , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Surgical Wound Infection/microbiology , Treatment Outcome , Young AdultABSTRACT
The purpose of the present work was to inform about the first case of meningitis associated to the bacteria Alcaligenes xylosoxidans in a patient with HIV/AIDS. The patient was a 46-year-old male, with the antecedent of have been diagnosed for HIV/ AIDS, who attended in the Hospital Universitario de Colima, Mexico, with fever, shock and meningismus. The study of the cerebrospinal fluid showed pleocytosis, elevated protein levels and hypoglycorrhachia. The culture yielded the presence of Alcaligenes xylosoxidans with sensitivity to ciprofloxacin. After 14 days of treatment with this antibiotic, the patient showed neurologic improvement and was able to continue with his outpatient antiretroviral treatment. The present case shows the importance of the inclusion of this bacterium in the differential diagnosis of the neurological infections in HIV/AIDS patients and emphasizes the importance of considering the bacterial meningitis in this population.
Subject(s)
Humans , Male , Middle Aged , AIDS-Related Opportunistic Infections/microbiology , Alcaligenes/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Meningitis, Bacterial/microbiology , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/drug therapy , Anti-Infective Agents/therapeutic use , Ciprofloxacin/therapeutic use , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapyABSTRACT
The purpose of the present work was to inform about the first case of meningitis associated to the bacteria Alcaligenes xylosoxidans in a patient with HIV/AIDS. The patient was a 46-year-old male, with the antecedent of have been diagnosed for HIV/ AIDS, who attended in the Hospital Universitario de Colima, Mexico, with fever, shock and meningismus. The study of the cerebrospinal fluid showed pleocytosis, elevated protein levels and hypoglycorrhachia. The culture yielded the presence of Alcaligenes xylosoxidans with sensitivity to ciprofloxacin. After 14 days of treatment with this antibiotic, the patient showed neurologic improvement and was able to continue with his outpatient antiretroviral treatment. The present case shows the importance of the inclusion of this bacterium in the differential diagnosis of the neurological infections in HIV/AIDS patients and emphasizes the importance of considering the bacterial meningitis in this population.