Oral Administration Following Subcutaneous Administration of FCV Vaccines Enhances Vaccine Efficacy against Challenge of a Highly Virulent Vs Feline Calicivirus

Feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. Highly virulent systemic strains of FCV (vs FCV) have been described. These vs FCV isolates cause characteristic edema, cutaneous ulcers and other clinical signs typically associated with FCV infection. Vs FCV isolates also cause high mortality even in previously vaccinated cats. We reported previously that the FCV serum cross-neutralization profile of cat serum generated using the oralnasal route of administration is broader than with subcutaneous administration (SC), as measured with a 26-FCV viral panel (Rong et al., Virus Research 122:95-108, 2006). In this report, we tested the in vivo ef- ficacy of the FCV vaccine, in a 4-way (FCV-FHV-FPV-FCp) format, by using a highly virulent vs FCV- 33585 as the challenge virus. Vaccines were administered as 2-dose subcutaneouly (SC/SC), or subcutaneously followed by orally (SC/Oral). The mortality induced by vs FCV-33585 in unvaccinated control cats was 78% (7 out of 9 cats). The mortality decreased to 44% (4 out of 9 cats) with cats vaccinated with the 4-way vaccine given SC/SC. However, when this vaccine was given SC/Oral, the mortality decreased to 10% (1 out of 10 cats). The clinical scores, calculated based on frequency and severity of various clinical signs, correlated with mortality data. These results demonstrated that oral administration of FCV vaccines, as the second dose following the first dose of subcutaneious administration, ehances FCV efficacy against challenge of a highly virulent vs FCV. We propose that not only oral vaccination offers convenience and needle-free inoculation, it also enhances FCV vaccine efficacy.

Clinical research progress of oral administration of traditional Chinese medicine in the treatment of dry eyes

Dry eye is a common and frequently occurring ophthalmology disease with complex etiology and easy recurrence.Oral administration of traditional Chinese medicine has the characteristicsof high curative effect and little toxic and side effect in the treatment of dry eye.This paper collates the domestic reported clinical studies on the oral administration of traditional Chinese medicine in the treatment of dry eye,which are discussed from four aspects:special prescription for specific disease,addition and subtraction of main prescription,treatment based on syndrome differentiation and proprietary Chinese medicine.The curative effect and advantages of traditional Chinese medicine in the treatment of dry eye are demonstrated,providing a reference for the treatment of dry eye in the future.

Pharmacokinetics of Milbemycin Oxime in Dogs Following Its Intravenous and Oral Administration

The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of the drug.

A Study on Early Biological Effects of Oral Administration of Terephthalic Acid in Rats

Rats were fed with foods containing various doses of terephthalic (TPA) for 8 weeks. General status was observed and biological indices(including urine,serum and bone) were determined after 1, 3 and 8 week administration.Differences in urine calcium, ammonia, PH and serum albumin between the treat groups and the control were significant. Marked correlation was found in these indices. No Change in N-acetyl-β-D-glucosaminidase (NAG),serum calcium,bone calcium, alkaline phosphatase and alanine transaminase was noted in the treat groups.It suggests that change of urine ammonium concentration may serve as a protective level in setting the TPA exposure limit.

Acute Toxicity of Aluminium Phosphide Following Oral Administration in Rats

Aluminium phosphide (AlP) is used as a fumigant and also sometimes misused for suicidal attempts in India, due to its easy availability. The effect of phosphine, the gas that is liberated when AlP comes in contact with moisture, is well documented in the literature. However, the effect of AlP in its native form on animal models is not well cited. In this study we examined the acute toxic effect of AlP in rats. Oral LD50 of AlP for male and female rats were found to be 14. 13 and 11. 89mg/kg, respectively. Oral administration of an AlP dose of 0. 80 LD50 resulted in significant increases in the level of plasma glutamic oxaloacetic transaminase,alkaline phosphatase, glucose and urea in rats of both sexes. Hemoglobin level and packed cell volume also increased significantly 6h after administration. Body weight was reduced but the organ to body weight ratio of lung, liver, spleen, kidney and testes remained unchanged.Histopathological changes induced by AlP during 24-48h induced hemorrhage, congestion and mild to moderate atrophy of various cellular components of visceral organs. The study showed that the acute toxic effect of AlP may be due to hypovolemic shock. Female rats were found to be more susceptible than were males.

Therapeutic Effect of Oral Administration and External Therapy of Traditional Chinese Medicine on Cervical Tuberculous Lymphadenopathy

Objective:To analyze the clinical effect and value of oral administration and external therapy of traditional Chinese medicine for treatment of cervical tuberculous lymphadenopathy.Methods:A total of 56 patients with cervical tuberculous lymphadenopathy admitted to our hospital from January 1 to January 2018 were recruited.By using double-blind method,the patients were divided into control group(n=28)and experimental group(n=28).Control group comprised of patients with conventional anti-tuberculosis treatment,while the experimental group comprised of patients treated with oral administration and external therapy of traditional Chinese medicine.Total effective rate,incidence of complication and level of T lymphocyte subsets were compared between the two groups of cervical tuberculous lymphadenopathy patients.Results:Post-treatment data of total effective rate,complication rate,CD3+,CD4+,CD8+,CD4+/CD8+of the experimental group were compared with the control group.P<0.05;statistical analysis showed statistical significance.Post-treatment data of CD3+,CD4+,CD8+,CD4+/CD8+of both control and experimental groups were compared with pre-treatment data.P<0.05;statistical analysis showed statistical significance.Conclusion:Oral administration and external therapy of traditional Chinese medicine possesses significant effect in treatment of cervical tuberculous lymphadenopathy.

Treatment of Irritable Bowel Syndrome by Oral Administration of Chinese Medicines and Retention-Enema——A Report of 50 Cases

Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.

The morphological changes in the internal organs of laboratory animals after prolonged oral administration of gold nanoparticles

Recently gold nanoparticles(GNPs)have been actively studied as photot hermal converters,drug carriers,and imaging agents in a wide range of applications in cancer diagnosis and ther apy.The prolonged peroral administration of GNPs in a range of sizes was performed to investigate the morphological changes and their reversibility in the internal organs of laboratory animals.In this study,GNP's with average diameters of 2 nm,15 nm and 50nm were administered during 30 days,and the reversibility of morphological changes was investigated 14 days after administration.After the prolonged administration of GNPs,the severity of morphological changes in the liver,kidney,spleen and lymph nodes depended on the nanoparticle size.Specifically,50 nm nano-particles caused the most pronounced dystrophic and necrobiotic effects,whereas the smallest 2 nm nanoparticles caused proliferative changes.Most importantly,the development of patho-logical processes was reversible,as evidenced by the gradual restoration of the organ structure at 14 days after the end of GNPs administration.

The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

A biodegradable poly(lactic-co-glycolic acid) loading atorvastatin calcium(AC) nanoparticles(AC-PLGA-NPs) were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGANPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

Pharmacokinetic Disposition of Streptomycin Sulfate in Japanese Eel (<i>Anguilla japonica</i>) after Oral and Intramuscular Administrations

Pharmacokinetics and residue elimination of streptomycin sulfate (STR) are important in the determination of optimal dosage regimens and in establishing safe withdrawal periods in farmed fishes. The pharmacokinetics of STR was studied after a single dose (50 mg/kg) of intramuscular (i.m.) or oral gavage (p.o.) administration to Japanese eel (Anguilla japonica) in freshwater at 25°C. Eight fish per sampling point were examined after treatment. Plasma and muscle were collected and analyzed by high-performance liquid chromatography (HPLC) method with 0.05 μg/ml detection limit. The data of pharmacokinetics conformed to the two-compartment open model for intramuscular and one-compartment open model for oral administrations. After intramuscular administration, the elimination half-life (t1/2β) was calculated to be 11.346 h, the maximum plasma concentration (Cmax) to be 29.524 μg/ml, the time to peak plasma streptomycin concentration (Tmax) to be 0.218 h, and the area under the plasma concentration-time curve (AUC) to be 90.206 μg/ml?h. Following p.o. administration, the corresponding estimates were 13.239 h, 0.346 μg/ml, 11.960 h, and 12.356 μg/ml?h. After intramuscular administration, a therapeutic concentration of the drug was maintained for 12 hours in the plasma, however, a therapeutic level could not be achieved after oral administration, and the results suggest that the drug can be used clinically by intramuscular administration against streptomycin susceptible systemic infections in Japanese eel.

Recent advances in particulate drug delivery systems: Oral, pulmonary, and ophthalmic administrations

Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system.

Systematic review on the adverse reactions of oral administration of Indigo Naturalis and its preparations

Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.

The 30-Day Oral Administration Studies of Liposoluble Tea Polyphenols in Rats

Tea polyphenols is a natural antioxidant with a variety of biological activity.However,the weak liposolubility and low bioavailability limit their application.As a result,structural modification of tea polyphenols comes into being.The prepared liposoluble tea polyphenols was suggested as a good candidate antioxidant for edible-oil and fats products.But,safety studies on liposoluble tea polyphenols are limited.The objective of the present study was conducted to synthesize liposoluble tea polyphenols and evaluate its toxicity in Sprague-Dawley rats on oral administration at dietary levels of 1,2 and 4% for 30 days.There were no adverse effects on general condition,growth,food intake,feed conversion efficiency,haematology parameters,clinical chemistry values and organ weights.High-dose males exhibited a higher haemoglobin concentration and a lower alanine aminotransferase levels,and high-dose females showed a lower albumin and globulin levels.These slight changes were considered of no toxicological significance.Necropsy and histopathology findings revealed no treatment-related changes in any of the organs.Thus,the results allowed us to conclude that the liposoluble tea polyphenols properly utilized in the oral administration could be devoid of any toxic risk.

Oral Hygiene in the Presence of Orthodontic Therapy

Orthodontic treatment offers great advantages in improving facial and smile aesthetics, self-confidence and the function of the stomatognathic apparatus. The pursuit of these advantages makes use of orthodontic appliances that could be fixed or removable. However, it’s worth stating that these appliances interfere with tooth brushing, making it more difficult to brush teeth effectively. Orthodontics appliances therefore promote the accumulation of dental plaque, which results in both quantitative and qualitative changes in the oral microbiota, hence, exposing patients to several adverse effects such as White spot lesions, dental caries, periodontal pathologies and halitosis. For this reason, oral assessment of patients before, during and after treatment is necessary as well as oral hygiene instructions and motivation. Orthodontists therefore, should educate patients on oral and periodontal hygiene in order to control dental and periodontal complications. Prescriptions of plaque control materials adapted to each patient are done in order to optimize the final result and minimize unwanted complications.

Optimal timing for the oral administration of DaCheng-Qi decoction based on the pharmacokinetic and pharmacodynamic targeting of the pancreas in rats with acute pancreatitis

AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction(DCQD) in rats with acute pancreatitis(AP) based on the pharmacokinetic and pharmacodynamic parameters.METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4 h G(a), 12 h G(a) and 24 h G(a)]. The NG(a) and model groups were administered DCQD(10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4 h G(b), 12 h G(b) and 24 h G(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared.RESULTS The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12 h G(a) group were higher than those in the 4 h G(a) group in the pancreatic tissues(P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values(AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12 h G(a) group were larger than those in the 4 h G(a) or 24 h G(a) groups. The 12 h G(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12 h G(b) and 24 h G(b) groups were higher than in the MG(b)s(96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24 h G(b) group, the IL-10 level was higher than in the other two treatment groups(251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4 h G(b) and 12 h G(b) groups compared to theMG(b)s(89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05). CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of antiinflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.

Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

Clinical Observation on Treatment of Acquired Paralytic Strabismus by Acupuncture Plus Oral Administration of Chinese Herbs

From June 1996 to June 2002, the author treated 38 cases of acquired paralytic strabismus by acupuncture plus oral administration of Zheng Rong Tang (正容汤), with another 38 cases of acquired paralytic strabismus treated only with oral administration of Chinese herbs as the controls. The results are reported as follows.

Clinical Study on Improving Articulation Clarity in Spastic Cerebral Palsy with 120 Cases of Oral-Facial Acupressure Combined with Oral Placement Therapy

Objective:To observe the efficacy of oral-facial acupressure combined with oral placement therapy(OPT)in improving articulation clarity in 120 children with spastic cerebral palsy,and to explore effective therapeutic solutions for speech disorders associated with spastic cerebral palsy.Methods:A total of 120 children with spastic cerebral palsy and speech disorders,meeting the inclusion criteria,were randomly assigned into two groups:60 cases in the treatment group and 60 cases in the control group.The treatment group received orofacial acupressure combined with OPT,while the control group received only OPT.The Oral Motor Function Assessment Scale(OMFAS),developed by the China Rehabilitation Research Centre(CRRC),was used to evaluate the treatment outcomes before and after the intervention.Results:After the treatment,both the treatment and control groups showed improved mobility of the mandible,lips,and tongue.However,the treatment group exhibited significantly better improvement than the control group,with the difference between the two groups being statistically significant(P<0.05).Conclusion:Oral-facial acupressure combined with OPT can effectively improve articulation clarity in children with spastic cerebral palsy.This combined therapy is recommended for clinical promotion and application.

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Investigation on taste characteristics and sensory perception of soft-boiled chicken during oral processing based on electronic tongue and electronic nose

The sensory perception of food is a dynamic process,which is closely related to the release of flavor substances during oral processing.It’s not only affected by the food material,but also subjected to the individual oral environment.To explore the oral processing characteristics of soft-boiled chicken,the sensory properties,texture,particle size,viscosity,characteristic values of electronic nose and tongue of different chicken samples were investigated.The correlation analysis showed that the physical characteristics especially the cohesiveness,springiness,resilience of the sample determined oral processing behavior.The addition of chicken skin played a role in lubrication during oral processing.The particle size of the bolus was heightened at the early stage,and the fluidity was enhanced in the end,which reduced the chewing time to the swallowing point and raised the aromatic compounds signal of electronic nose.But the effect of chicken skin on chicken thigh with relatively high fat content,was opposite in electronic nose,which had a certain masking effect on the perception of umami and sweet taste.In conclusion,fat played a critical role in chicken oral processing and chicken thigh had obvious advantages in comprehensive evaluation of soft-boiled chicken,which was more popular among people.