Role of honey after tonsillectomy: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Honey reduced post-tonsillectomy pain, but its effects on awakening at night, inflammation and healing of the tonsillar fossa were controversial. OBJECTIVES: This systematic review and meta-analysis of randomised controlled trials (RCTs) evaluated the effect of oral honey on pain, consumption of painkillers, awakening at night, healing of tonsillar fossa and adverse effects in children after tonsillectomy. METHODS: A search of MEDLINE, EMBASE, Scopus, CINAHL and Cochrane Collaboration Library databases was performed without any restriction of publication year. The end date of search was 30 June 2016. The search was supplemented by search from Google, hand search of cross-references of selected articles and reviews, and contacting the authors of different studies. The inclusion criteria were RCTs comparing the effect of honey with control on different outcomes, in children after tonsillectomy. RESULTS: Our search generated 64 studies, and eight RCTs met our inclusion criteria. The methodological quality of RCTs was poor. Compared to control, honey significantly decreased postoperative pain from day 1 to day 7 (P = 0.05 to <0.0001); consumption of painkillers from days 1 to 5 (P = 0.03 to 0.003) and on day 10 (P = 0.002); and number of awakening at night due to pain on days 2 and 4 after tonsillectomy (P = 0.0001, 0.004). The healing of tonsillar fossa was significantly greater with honey compared to control on days 3-4 (P = 0.02) and days ≥9 (P = 0.01) after tonsillectomy. The adverse effects were not significantly different between honey and control groups. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) of the evidence for different outcomes varied from 'low' to 'very low'. CONCLUSIONS: Honey improved pain, requirement of painkillers and awakening at night due to pain in children after tonsillectomy. There was little improvement in healing of tonsillar fossa. The GRADE of the evidence varied from 'low' to 'very low'. A good-quality, placebo-controlled RCT of different doses and durations of administration of honey is required to evaluate its clear efficacy and safety in children after tonsillectomy.

A review of recent developments in buffalo reproduction - a review.

The buffalo is an important livestock resource in several countries of South Asia and the Mediterranean regions. However, reproductive efficiency is compromised due to known problems of biological and management origins, such as lack of animal selection and poor nutrition. Under optimal conditions puberty is attained at 15 to 18 months in river buffalo, 21 to 24 months in swamp buffalo and is influenced by genotype, nutrition, management and climate. However, under field conditions these values deteriorate up to a significant extant. To improve reproductive efficiency, several protocols of oestrus and ovulation synchronization have been adopted from their use in commercial cattle production. These protocols yield encouraging pregnancy rates of (30% to 50%), which are comparable to those achieved in buffaloes bred at natural oestrus. The use of sexed semen in buffalo heifers also showed promising pregnancy rates (50%) when compared with conventional non-sexed semen. Assisted reproductive technologies have been transferred and adapted to buffalo but the efficiency of these technologies are low. However, these latest technologies offer the opportunity to accelerate the genetic gain in the buffalo industry after improving the technology and reducing its cost. Most buffaloes are kept under the small holder farming system in developing countries. Hence, future research should focus on simple, adoptable and impact- oriented approaches which identify the factors determining low fertility and oestrus behaviour in this species. Furthermore, role of kisspeptin needs to be explored in buffalo.

Urotensin I-like immunoreactivity in amacrine cells of the goldfish retina.

Urotensin I-like immunoreactivity (UILI), in different localization from that of corticotropin releasing factor-like immunoreactivity (CRFLI), in the goldfish retina has been demonstrated by means of radioimmunoassay, high-performance liquid chromatography (HPLC) and immunohistochemistry. Radioimmunoassay showed 350 +/- 40 pg/mg prot. of UILI in goldfish retina extracts. The immunoreactive material present in the retina was also characterized by reversed phase HPLC. Some of the UILI co-eluted with synthetic carp UI, though the HPLC experiments suggested the existence of other UILI substance(s) with less hydrophobicity than synthetic UI. By immunohistochemistry, UILI and CRFLI were seen in different amacrine cells of the goldfish retina. It is suggested that UI may be involved in the fish visual transmission system together with CRF and other neuropeptides.

Estrus synchronization with lower dose of PGF2 alpha and subsequent fertility in subestrous buffalo.

Two experiments were conducted to determine luteal regression, estrous response and fertility in buffalo receiving cloprostenol via 2 routes of administration. In Experiment 1, cyclic buffalo (n = 10) were assigned to 2 equal groups receiving either 500 micrograms i.m. cloprostenol (Estrumate, ICI) or 125 micrograms cloprostenol injected intravulvosubmucosal (ivsm) ipsilateral to the side of the corpus luteum (CL) on Day 11 of an induced estrous cycle. Serum progesterone (P4) concentrations were evaluated immediately before treatment and at 24, 48, 72, 96 and 120 h after PGF2 alpha administration. The decline in serum P4 concentrations was significantly different (P < 0.05) between groups up to 48 hrs after treatment. However, no significant difference (P > 0.05) was observed for the interval from treatment to the onset of estrus (94.9 +/- 10.7 vs 96.0 +/- 15.9 h) for 500 or 125 micrograms of cloprostenol groups, respectively. In Experiment 2, multiparous, lactating subestrous buffaloes (n = 137) were treated either with 125 micrograms ivsm cloprostenol or 500 micrograms i.m. cloprostenol (n = 28 vs 33, respectively) during peak breeding (September-February) or low breeding (March-August) season (n = 37 vs 39, respectively). Buffalo observed in estrus were inseminated twice with frozen-thawed semen at 12 and 22 h after the onset of estrus. Buffalo that failed to exhibit estrus were given a second equal dose of cloprostenol at an 11-d interval and underwent fixed-time insemination at 72 and 96 h. The interval to the onset of estrus was 85.0 +/- 4.4 vs 73.2 +/- 2.6 h during peak breeding and 96.1 +/- 2.6 vs 92.1 +/- 3.8 h during the low breeding season for buffalo treated with 125 and 500 micrograms cloprostenol, respectively. These intervals were different (P < 0.05) between seasons but not between treatments in the same season. Conception rates of 47.8 vs 53.1% during peak breeding and 23.5 vs 25.6% during low breeding season were also different (P < 0.05) between seasons but not between the treatments in the same season for buffalo treated with 125 and 500 micrograms cloprostenol, respectively. These results indicated that 125 micrograms ivsm and 500 micrograms i.m. cloprostenol were equally effective for synchronizing estrus in subestrous buffalo. No negative effect of a lower dose of cloprostenol was observed on estrus synchrony and subsequent fertility; however, season of treatment had a significant effect on conception rates.

Studies on the mechanism of action of alpha-monochlorohydrin.

After a single oral dose of 100 mg/kg of alpha-chlorohydrine, two distinct phases in the response of the testes to the treatment have been observed: (i) the immediate onset of testicular swelling lasting up to five days, accompanied with a steady increase in the weight of the testes and (ii) thereafter a constant decrease in the testes weight. Changes in the diameter of the seminiferous tubules and the thickness of the basement membrane were observed after the administration of the drug. Multinucleated giant cells were encountered 5 days after drug administration. Alkaline phosphatase, SDH, nucleic acids and proteins showed a fall after treatment with the drug. On the contrary, cholesterol, phospholipids and glycogen showed an increase after its administration. Acid phosphatase showed a fall in the initial stages only, but the activity was higher after 10, 20 and 40 days of the treatment with the drug. The level of plasma and testes testosterone remained normal after chlorohydrin administration. The induction of lesions in hypophysectomised gonadotropin-stimulated animals suggests that the action of chlorohydrin is not mediated through gonadotropins. Alpha-chlorohydrin administered intratesticularly did not evoke any changes in the histo-architecture of the testis.

Sequential histopathological and biochemical events in rat caput epididymis after alpha monochlorohydrin administration.

This paper presents sequential histological, histochemical and biochemical changes in rat caput epididymis after a single 100 mg/kg oral dose of alpha chlorohydrin. Desquamation of caput epithelium occurs as early as two days after drug treatment. The caput epididymis is blocked because of accumulation of testicular fluid containing exfoliated immature testicular cells and caput epithelium. There was no effect of drug on motility and morphology of spermatozoa examined from different segments of epididymis and vas deferens. Marked decrease in acid and alkaline phosphatases, nucleic acids and proteins have been registered after drug treatment. On the contrary increase in SDH, cholesterol and glycogen was observed after drug treatment. Decrease in phospholipids in initial stages has also been observed.

PIP: The histological, histochemical, and biochemical effects of a single 100 mg/kg oral dose of alpha-chlorohydrin on the caput epididymis of the rat were studied. Within 2 days of treatment, evidence of desquamation of the caput epithelium became apparent. The accumulation of testicular fluid, which contained exfoliated immature testicular cells and caput epithelium, caused blockage of the caput epididymis. However, spermatoz oa recovered from different regions of the epididymis and vas deferens did not exhibit altered motility or morphology. The treatment was associated with a decrease in caput epididymal content of acid alkaline phosphatases, nucleic acids and proteins, and an increase in SDH, cholesterol, and glycogen. Phospholipids were also decreased during the early stages after treatment. The results are discussed in relation to previous explanations of the mechanism of action of alpha-chlorohydrin.

Evaluation of chromatin integrity in human sperm using acridine orange staining with different fixatives and after cryopreservation.

Staining of cells with acridine orange (AO) has been widely accepted as a predictor of DNA damage in many cell types. Because of variability of protocols used in previous studies, the AO staining technique has not been widely accepted as a screening test to predict DNA damage in human sperm. In order to further validate the use of AO staining, sperm were evaluated using numerous variations in the staining protocol. This study also elucidated the effects of cryopreservation on sperm DNA. Sperm fixation in Carnoy's solution showed significantly (P < 0.05) more DNA damage (29.9 +/- 4.5%) than 2% glutaraldehyde (14.4 +/- 2.1%), 4% paraformaldehyde (5.5 +/- 1.7%), no fixation (15.8 +/- 4.3%) but did not differ from Diff Quik solution (19.2 +/- 5.8%). No difference was observed for sperm DNA damage assessment using a 0.2 m (15.5 +/- 3.2%) or 0.3 m (14.9 +/- 3.3%) concentration of Na(2)HPO(4).7H(2)O in the AO staining solution. Frozen-thawed semen samples showed increased damage to sperm DNA under both Carnoy's (fresh: 10.9 +/- 1.3%; frozen: 30.8 +/- 2.9%; P < 0.05) and Diff Quik fixation (fresh: 6.2 +/- 0.8; frozen: 17.1 +/- 2.5%P < 0.05). Present data also showed that spermatozoa from some individuals are more prone to DNA damage after freezing and thawing procedures than others. In conclusion, Carnoy's fixative provides a better predictive value for DNA damage to sperm using AO staining. Additionally, cryopreservation increased damage to the sperm DNA.

Segregation of FMRF amide-immunoreactive efferent fibers from NPY-immunoreactive amacrine cells in goldfish retina.

Immunocytochemical studies were conducted on goldfish to determine whether a retinal efferent fiber system, immunoreactive to the tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRFamide), might contain instead a substance similar to one of the 36-amino acid pancreatic polypeptides, the C-terminus of which is similar to FMRFamide. Our results demonstrate the presence of two separate peptidergic systems, one containing FMRFamide-like, and the other pancreatic polypeptide-like peptides. Antisera to FMRF amide reveal the efferent fibers, whose axons exit the optic nerve and terminate in layer 1 of the inner plexiform layer, as previously described. Antisera to porcine neuropeptide Y, and to avian and bovine pancreatic polypeptides label a sparse population of putative amacrine cell bodies and a dense fiber plexus in layers 1, 3, and 5 of the inner plexiform layer. Based on intensity of staining, this amacrine cell peptide appears to be most similar to neuropeptide-Y. Radioimmunoassay and immunocytochemical staining of retinas in which the efferent fiber peptide was depleted by optic nerve crush confirm in large part the observation that the two peptide systems are distinct. However, there is some cross-recognition of the FMRF amide-like tissue antigen by pancreatic polypeptide antibodies. Double-label studies with antisera to tyrosine hydroxylase and neuropeptide-Y indicate that the pancreatic polypeptide antigen is not co-localized with catecholamines.

The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast.

Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase.

Cdc42Hs is a member of the Ras superfamily of GTPases and initiates a cascade that begins with the activation of several kinases, including p21-activated kinase (PAK). We have previously used a 46 amino acid fragment of PAK (PBD46) to define the binding surface on Cdc42Hs [Guo et al. (1998) Biochemistry 37, 14030-14037]. Here we describe the three-dimensional solution structure of the Cdc42Hs. GMPPCP-PBD46 complex. Heteronuclear NMR methods were used to assign resonances in the complex, and approximately 2400 distance and dihedral restraints were used to calculate a set of 20 structures using a combination of distance geometry, simulated annealing, and chemical shift and Ramachandran refinement. The overall structure of Cdc42Hs in the complex differs from the uncomplexed structure in two major aspects: (1) the first alpha helix is reoriented to accommodate the binding of the peptide and (2) the regions corresponding to switch I and switch II are less disordered. As suggested by our previous work (Guo et al., 1998) and similar to the complex between Cdc42Hs and fACK [Mott et al. (1999) Nature 399, 384-388], PBD46 forms an intermolecular beta-sheet with beta2 of Cdc42Hs and contacts both switch I and switch II. The extensive binding surface between PBD46 and Cdc42Hs can account for both the high affinity of the complex and the inhibition by PBD46 of GTP hydrolysis.

Cysteine mutagenesis and homology modeling of the ligand-binding site of a kainate-binding protein.

Glutamate receptors comprise the most abundant group of neurotransmitter receptors in the vertebrate central nervous system. Cysteine mutagenesis in combination with homology modeling has been used to study the determinants of kainate binding in a glutamate receptor subtype, a low molecular weight goldfish kainate-binding protein, GFKARbeta. A construct of GFKARbeta with no cysteines in the extracellular domain was produced, and single cysteine residues were introduced at selected positions. N-Ethylmaleimide or derivatized methanethiosulfonate reagents (neutral or charged) were used to modify the introduced cysteines covalently, and the effect on [(3)H]kainate binding was determined. In addition, cysteine mutants of GFKARbeta transiently expressed in HEK293 cells were labeled with a membrane-impermeable biotinylating reagent followed by precipitation with streptavidin beads and specific detection of GFKARbeta by Western blot analysis. The results are consistent with the proposal that the energy driving kainate binding is contributed both from residues within the binding site and from interactions between two regions (i.e. two lobes) of the protein that are brought into contact upon ligand binding in a manner analogous to that seen in bacterial amino acid-binding proteins.

Differential coupling through Val-344 and Tyr-442 of trimethylamine dehydrogenase in electron transfer reactions with ferricenium ions and electron transferring flavoprotein.

Modeling studies of the trimethylamine dehydrogenase-electron transferring flavoprotein (TMADH-ETF) electron transfer complex have suggested potential roles for Val-344 and Tyr-442, found on the surface of TMADH, in electronic coupling between the 4Fe-4S center of TMADH and the FAD of ETF. The importance of these residues in electron transfer, both to ETF and to the artificial electron acceptor, ferricenium (Fc(+)), has been studied by site-directed mutagenesis and stopped-flow spectroscopy. Reduction of the 6-(S)-cysteinyl FMN in TMADH is not affected by mutation of either Tyr-442 or Val-344 to a variety of alternate side chains, although there are modest changes in the rate of internal electron transfer from the 6-(S)-cysteinyl FMN to the 4Fe-4S center. The kinetics of electron transfer from the 4Fe-4S center to Fc(+) are sensitive to mutations at position 344. The introduction of smaller side chains (Ala-344, Cys-344, and Gly-344) leads to enhanced rates of electron transfer, and likely reflects shortened electron transfer "pathways" from the 4Fe-4S center to Fc(+). The introduction of larger side chains (Ile-344 and Tyr-344) reduces substantially the rate of electron transfer to Fc(+). Electron transfer to ETF is not affected, to any large extent, by mutation of Val-344. In contrast, mutation of Tyr-442 to Phe, Leu, Cys, and Gly leads to major reductions in the rate of electron transfer to ETF, but not to Fc(+). The data indicate that electron transfer to Fc(+) is via the shortest pathway from the 4Fe-4S center of TMADH to the surface of the enzyme. Val-344 is located at the end of this pathway at the bottom of a small groove on the surface of TMADH, and Fc(+) can penetrate this groove to facilitate good electronic coupling with the 4Fe-4S center. With ETF as an electron acceptor, the observed rate of electron transfer is substantially reduced on mutation of Tyr-442, but not Val-344. We conclude that the flavin of ETF does not penetrate fully the groove on the surface of TMADH, and that electron transfer from the 4Fe-4S center to ETF may involve a longer pathway involving Tyr-442. Mutation of Tyr-442 likely disrupts electron transfer by perturbing the interaction geometry of TMADH and ETF in the productive electron transfer complex, leading to less efficient coupling between the redox centers.

Evidence for FMRF-amide as a neurotransmitter in the gill of Aplysia californica.

In Aplysia californica, multiple regulatory mechanisms are involved in the actions of neurotransmitters on the gill. Neurotransmitter receptors and adenylate cyclase were examined in a particulate fraction of gill homogenates. The neuropeptide FMRF-amide stimulated enzyme activity 7- to 8-fold (EC50, 1 microM) via receptors that were pharmacologically distinct from those for dopamine and serotonin. FMRF-amide augmented cyclic AMP levels in slices of gill tissue with a time course similar to that for adenylate cyclase activation. Increases in cyclic AMP levels produced by the neuropeptide were potentiated by the phosphodiesterase inhibitor theophylline. Physiological responses to neuropeptides and cyclic AMP analogues were examined in a perfused, isolated gill preparation. Phasic contractions evoked by FMRF-amide (EC50, 0.1 microM) were mimicked by membrane-permeable analogues of cyclic AMP. Comparison of FMRF-amide effects on adenylate cyclase and gill behavior suggests an association between cyclic AMP and phasic contractions. In addition, FMRF-amide-like immunoreactivity, detected by antisera raised against the neuropeptide, was found in nerve fibers innervating the gill. These findings indicate that in Aplysia, FMRF-amide or a closely related peptide neurotransmitter may be involved in the physiological regulation of gill behavior.

Protein dynamics enhance electronic coupling in electron transfer complexes.

Electron-transferring flavoproteins (ETFs) from human and Paracoccus denitrificans have been analyzed by small angle x-ray scattering, showing that neither molecule exists in a rigid conformation in solution. Both ETFs sample a range of conformations corresponding to a large rotation of domain II with respect to domains I and III. A model of the human ETF.medium chain acyl-CoA dehydrogenase complex, consistent with x-ray scattering data, indicates that optimal electron transfer requires domain II of ETF to rotate by approximately 30 to 50 degrees toward domain I relative to its position in the x-ray structure. Domain motion establishes a new "robust engineering principle" for electron transfer complexes, tolerating multiple configurations of the complex while retaining efficient electron transfer.