scholarly journals Effect of antihistaminics on amplitude of rabbit gut

2017 ◽  
Vol 5 (5) ◽  
pp. 1927
Author(s):  
Rashmi Prakash ◽  
Vinay Singh ◽  
Devesh Kumar ◽  
Jamal Haider ◽  
A. B. Asthana ◽  
...  
Keyword(s):  
Small Intestine ◽  
First Generation ◽  
Second Generation ◽  
In Vitro Study ◽  
Organ Bath ◽  
Chlorpheniramine Maleate ◽  
Motor Patterns ◽  
Gut Motility ◽  
Antihistaminic Drug

Background: The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents too.Methods: In vitro study is done to explore the effect of 1st generation antihistaminic (chlorpheniramine maleate) and second generation antihistaminic (Fexofenadine) on amplitude of gut motility by isolated rabbit gut preparation on Dale’s Organ bath, part of terminal ileum is used for study. Eight rabbits weighing 2 to 4.5 kg were used for study. The effect of antihistaminic observed that both drugs reduce amplitude.Results: The effect of Chlorpheniramine malete and Fexofenadine on amplitude observed and it found that both decrease the amplitude significantly.Conclusions: This study establishes a correlation between amplitude of gut and effect of antihistaminic suggests that antihistaminic drug both first generation and second generation decreases the amplitude of gut motility with a significant response.

scholarly journals Identification of Novel Mutations Responsible for Resistance to MK-2048, a Second-Generation HIV-1 Integrase Inhibitor

2010 ◽  
Vol 84 (18) ◽  
pp. 9210-9216 ◽  
Author(s):  
Tamara Bar-Magen ◽  
Richard D. Sloan ◽  
Daniel A. Donahue ◽  
Björn D. Kuhl ◽  
Alexandra Zabeida ◽  
...  
Keyword(s):  
Viral Replication ◽  
First Generation ◽  
Second Generation ◽  
Integrase Inhibitor ◽  
Replication Capacity ◽  
Strand Transfer ◽  
Viral Replication Capacity ◽  
Transfer Inhibitor ◽  
Potential Basis

ABSTRACT MK-2048 represents a prototype second-generation integrase strand transfer inhibitor (INSTI) developed with the goal of retaining activity against viruses containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. These mutations were selected in vitro and confirmed by site-specific mutagenesis. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. The subsequent selection of E138K partially restored replication capacity to ≈13% of wt levels and increased resistance to MK-2048 to ≈8-fold. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer “off” rate of MK-2048. In silico structural analysis suggests that the introduction of a positively charged arginine at position 118, near the catalytic amino acid 116, might decrease Mg2+ binding, compromising enzyme function and thus leading to the significant reduction in both integration and viral replication capacity observed with these mutations.

212 INSEMINATION OF OVUM PICKUP-DERIVED DAIRY COWS RESULTS IN OFFSPRING WITH NORMAL BIRTH WEIGHT

2008 ◽  
Vol 20 (1) ◽  
pp. 185
Author(s):  
E. Mullaart ◽  
B. Landman ◽  
J. S. Merton
Keyword(s):  
Birth Weight ◽  
First Generation ◽  
Second Generation ◽  
Calf Serum ◽  
Control Group ◽  
High Birth Weight ◽  
Gestation Length ◽  
Aberrant Methylation ◽  
Epigenetic Changes

Animals derived by ovum pickup-in vitro production (OPU-IVP) have a higher birth weight compared with animals derived by AI (Wagtendonk et al. 2000 Theriogenology 53, 575–597). It has been suggested that this higher birth weight is the result of epigenetic changes such as aberrant methylation and gene expression pattern, which are caused by the presence of serum in the culture medium (Wrenzycki et al. 2004 Anim. Reprod. Sci. 82–83, 593–603). The present study aimed to investigate whether the higher birth weight, possibly caused by epigenetic changes, is a permanent characteristic that is transmitted to the offspring. We therefore monitored the birth weight of calves born after insemination of OPU-IVP-derived animals. Ovum pickup-IVP was performed according to routine procedures. Immature COC were recovered by OPU. The COC were matured in vitro in TCM-199 supplemented with fetal calf serum (FCS)/LH/FSH. Subsequently, matured oocytes were fertilized with frozen–thawed gradient-separated semen and further cultured for 7 days in TCM-199/10% FCS on a BRL monolayer (CoCul group) or in SOFaaBSA (SOF group). First-generation OPU-IVP animals were produced from oocytes collected by OPU of AI-derived animals. The second generation was produced by inseminating OPU-IVP animals. Calves generated by inseminating AI animals were used as a control group. Birth weights of control AI, first-generation, and second-generation calves were analyzed by using restricted maximum likelihood (Genstat 9.1). Model Birth Weight: *Fixed: Parity Recipient + Sex + Gestation Length + Year + Embryo Type (AI, first, or second generation) + Culture System (CoCul or SOF). *Random: Sire + Barn. The results (Table 1) clearly show that the first-generation (OPU-IVP) calves had, on average, a 3.4-kg greater birth weight than the AI calves. The second-generation calves, however, had approximately the same birth weight as the calves in the AI control group. Our results indicated that the high birth weight of OPU-IVP-derived calves is not a permanent characteristic that is transmitted to their offspring. Previous studies have demonstrated that the fertility of OPU-IVP-derived animals is in the normal range (Wagtendonk et al. 2000 Theriogenology 53, 575–597). Table 1. Birth weight (least squares means ± SE) of AI calves (control), first generation OPU-IVP-derived calves, and second generation AI derived calves from OPU-IVP mothers

Development of the sheep–canid cycle of Sarcocystis tenella

1982 ◽  
Vol 60 (10) ◽  
pp. 2464-2477 ◽  
Author(s):  
J. P. Dubey ◽  
C. A. Speer ◽  
G. Callis ◽  
J. A. Blixt
Keyword(s):  
Small Intestine ◽  
Blood Vessels ◽  
Peripheral Blood ◽  
First Generation ◽  
Second Generation ◽  
Mesenteric Arteries ◽  
Infected Meat ◽  
Small Intestines ◽  
Sarcocystis Tenella

Thirty-seven sheep were inoculated orally with 104 to 66 × 106Sarcocystis tenella sporocysts from dogs or coyotes and necropsied between 1 and 276 days postinoculation (DPI). Two single zoites were found in submucosal arteries of small intestines of lambs 3 and 6 DPI. At 9 to 21 DPI, numerous first-generation meronts were found in mesenteric arteries, intestinal blood vessels, and occasionally in other organs. First-generation meronts were 37.0 × 27.3 μm in sections and 54.4 × 46.6 μm in smears. At 16 to 40 DPI, second-generation meronts were found in capillaries of several organs; renal meronts were 20.6 × 12.0 μm in sections. Merozoites were found in peripheral blood at 14 to 16 DPI and at 25 to 32 DPI. Earliest sarcocysts were found at 35 DPI and contained one to three metrocytes. At 40 DPI, sarcocysts were up to 97 × 10 μm and contained 1 to 13 metrocytes. Bradyzoites formed between 52 and 66 DPI. At 75 DPI, sarcocysts had cross-striated walls and were infective for coyotes. Dogs and coyotes fed infected meat shed sporocysts in feces 9 to 10 days later. Gamonts were found in the small intestine between 8 and 21 h postinoculation and sporulation was completed within 8 days.

Besnoitia neotomofelisn. sp. (Protozoa: Apicomplexa) from the southern plains woodrat (Neotoma micropus)

Parasitology ◽  
2010 ◽  
Vol 137 (12) ◽  
pp. 1731-1747 ◽  
Author(s):  
J. P. DUBEY ◽  
M. J. YABSLEY
Keyword(s):  
Small Intestine ◽  
First Generation ◽  
Mesenteric Lymph Nodes ◽  
Highly Pathogenic ◽  
Southern Plains ◽  
African Green Monkey Kidney ◽  
Tissue Sections ◽  
A New Species

SUMMARYCertain species of the protozoan genusBesnoitiacause clinical disease in livestock and wildlife. In the present paper a new species,Besnoitia neotomofelisis described from the southern planes woodrat (Neotoma micropus). The parasite was detected by bioassay of woodrat tissues in outbred Swiss Webster mice in an attempt to isolateToxoplasma gondii. Initially, the organism was misdiagnosed asT. gondiibecause it was highly pathogenic for mice and its tachyzoites resembledT. gondiitachyzoites. Further studies revealed that it differed structurally and biologically fromT. gondii.Tachyzoites were successfully cultivated and maintainedin vitroin bovine monocytes and African green monkey kidney cells, andin vivoin mice. Non-dividing, uninucleate tachyzoites were approximately 1×5μm in size. Longitudinally-cut bradyzoites in tissue sections measured 1·5–1·6×7·7–9·3μm. Tissue cysts were microscopic, up to 210μm long, and were infective orally to mice. Cats fed tissue cysts shed unsporulated 13×14μm sized oocysts. All mice inoculated withB. neotomofelisdied of acute besnoitiosis, irrespective of the dose, and Norwegian rats became infected but remained asymptomatic. Entero-epithelial stages (schizonts, gamonts) were found in cats fed tissue cysts. Large (up to 40×50μm) first-generation schizonts developed in the lamina propria of the small intestine of cats. A second generation of small sized (8μm) schizonts containing 4–8 merozoites was detected in enterocytes of the small intestine. Gamonts and oocysts were seen in goblet cells of the small intestinal epithelium. Tachyzoites were present in mesenteric lymph nodes of cats. Phylogenetic analysis indicated thatB. neotomofeliswas related to otherBesnoitiaspecies from rodents, rabbits, and opossums.Besnoitia neotomofelisis distinct from the 3 other species ofBesnoitia, B. wallacei, B. darlingiandB. oryctofelisithat utilize cats as a definitive host.

Characterization of motor patterns in isolated human colon: are there differences in patients with slow-transit constipation?

2012 ◽  
Vol 302 (1) ◽  
pp. G34-G43 ◽  
Author(s):  
Nick J. Spencer ◽  
Melinda Kyloh ◽  
David A. Wattchow ◽  
Anthony Thomas ◽  
Tiong Cheng Sia ◽  
...  
Keyword(s):  
Muscle Tension ◽  
Human Colon ◽  
Slow Transit Constipation ◽  
Organ Bath ◽  
Motor Patterns ◽  
Slow Transit ◽  
Descending Colon ◽  
Transit Constipation

The patterns of motor activity that exist in isolated full-length human colon have not been described. Our aim was to characterize the spontaneous motor patterns in isolated human colon and determine whether these patterns are different in whole colons obtained from patients with slow-transit constipation (STC). The entire colon (excluding the anus), was removed from patients with confirmed STC and mounted longitudinally in an organ bath ∼120 cm in length, containing oxygenated Krebs' solution at 36°C. Changes in circular muscle tension were recorded from multiple sites simultaneously along the length of colon, by use of isometric force transducers. Recordings from isolated colons from non-STC patients revealed cyclical colonic motor complexes (CMCs) in 11 of 17 colons, with a mean interval and half-duration of contractions of 4.0 ± 0.6 min and 51.5 ± 15 s, respectively. In the remaining six colons, spontaneous irregular phasic contractions occurred without CMCs. Interestingly, in STC patients robust CMCs were still recorded, although their CMC pacemaker frequencies were slower. Intraluminal balloon distension of the ascending or descending colon evoked an ascending excitatory reflex contraction, or evoked CMC, in 8 of 30 trials from non-STC (control) colons, but not from colons obtained from STC patients. In many control segments of descending colon, spontaneous CMCs consisted of simultaneous ascending excitatory and descending inhibitory phases. In summary, CMCs can be recorded from isolated human colon, in vitro, but their intrinsic pacemaker frequency is considerably faster in vitro compared with previous human recordings of CMCs in vivo. The observation that CMCs occur in whole colons removed from STC patients suggests that the intrinsic pacemaker mechanisms underlying their generation and propagation are preserved in vitro, despite impaired transit along these same regions in vivo.

Effect of Mechanical Length Oscillations on Airways Smooth Muscle Reactivity and Crossbridge Cycling

2011 ◽  
Author(s):  
P. Mbikou ◽  
A. M. Al-Jumaily
Keyword(s):  
In Vitro Study ◽  
Relaxation Effect ◽  
Organ Bath ◽  
Active Force ◽  
Immunofluorescence Technique ◽  
Cholinergic Stimulation ◽  
Airways Smooth Muscle ◽  
Crossbridge Cycle ◽  
Optimal Effect

Superimposition of length fluctuations on contracted ASM have shown to reduce active force and stiffness. This effect is usually attributed to disruption of the actomyosin crossbridge cycle; however no direct experimental data is available to support this hypothesis. This in vitro study investigated the effect of the mechanical strains on 1) the ASM reactivity and 2) on the actin-myosin crossbridges. Experiments were carried out on maximally contracted bovine ASM subjected to length strains at various frequency in the range from 10 to 100Hz, superimposed on normal tidal stretches (frequency 0.33Hz, amplitude 4%). An organ bath system was used to apply strains and measure the force; immunofluorescence technique was performed to assess the crossbridges. The results show that superimposed length strains increase breathing relaxation effect with an optimal effect obtained at 50Hz. The cholinergic stimulation promotes actin-myosin connection, and length stretches promote the detachment of those crossbridges.

Insights into mechanisms of intestinal segmentation in guinea pigs: a combined computational modeling and in vitro study

2008 ◽  
Vol 295 (3) ◽  
pp. G534-G541 ◽  
Author(s):  
Jordan D. Chambers ◽  
Joel C. Bornstein ◽  
Evan A. Thomas
Keyword(s):  
Guinea Pig ◽  
Computational Model ◽  
In Vitro Study ◽  
Afferent Pathway ◽  
Synaptic Coupling ◽  
Descending Pathways ◽  
Motor Patterns ◽  
Reflex Pathways ◽  
Vitro Model

Segmentation in the guinea pig small intestine consists of a number of discrete motor patterns including rhythmic stationary contractions that occur episodically at specific locations along the intestine. The enteric nervous system regulates segmentation, but the exact circuit is unknown. Using simple computer models, we investigated possible circuits. Our computational model simulated the mean neuron firing rate in the feedforward ascending and descending reflex pathways. A stimulus-evoked pacemaker was located in the afferent pathway or in a feedforward pathway. Output of the feedforward pathways was fed into a simple model to determine the response of the muscle. Predictions were verified in vitro by using guinea pig jejunum, in which segmentation was induced with luminal fatty acid. In the computational model, local stimuli produced an oral contraction and anal dilation, similar to in vitro responses to local distension, but did not produce segmentation. When the stimulus was distributed, representing a nutrient load, the result was either a tonic response or globally synchronized oscillations. However, when we introduced local variations in synaptic coupling, stationary contractions occurred around these locations. This predicts that severing the ascending and descending pathways will induce stationary contractions. An acute lesion in our in vitro model significantly increased the number of stationary contractions immediately oral and anal to the lesion. Our results suggest that spatially localized rhythmic contractions arise from a local imbalance between ascending excitatory and descending inhibitory muscle inputs and require a distributed stimulus and a rhythm generator in the afferent pathway.

scholarly journals Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Lovepreet Singh ◽  
Diana Fontinha ◽  
Denise Francisco ◽  
Miguel Prudêncio ◽  
Kamaljit Singh
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Blood Stage ◽  
Antiplasmodial Activity ◽  
Vector Borne Diseases ◽  
Insecticidal Effect ◽  
Successful Isolation ◽  
Molecular Hybrids

AbstractWith its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.

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