Recent Strategies for Ocular Drug Delivery: Promises and Challenges

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers. The emerging nanoscience is playing an important role in the development of novel strategies for ocular disease management. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and interact with certain ocular tissues. In this chapter, highlights will be made on barrier to intraocular delivery, general pathways for ocular absorption, and factors affecting intraocular bioavailability. The recent attempts of nanotechnology for treating anterior and posterior ocular diseases will be explored. This will include nanomicelles, nanoparticles, nanosuspensions, vesicular systems, in situ gel, dendrimers, contact lenses, implants, microneedles, and cell-based delivery systems. In addition, gene-based ocular delivery systems will be discussed. In this chapter, we will also provide a comprehensive overview of drug-device combinations used for ocular diseases such as glaucoma, dry eye disease, infections, and inflammations. Furthermore, drug delivery devices for ocular surgeries are discussed. Finally, challenges and future prospective of ocular delivery systems will be explored

Acaricidal activity of Foeniculum vulgare against Rhipicephalus annulatus is mainly dependent on its constituent from trans-anethone

Globally, the economic losses due to hard ticks infestation and the control of the associated diseases have been calculated at USD $13.9-18.7 billion per year. The economic impact is related to its direct damage to the skins, blood loss, anemia, severe immunological reactions and indirect losses that related to the effects of hemoparasites, cost of treatment for clinical cases and expenses incurred in the control of ticks. The current study evaluated the acaricidal activities of fennel Foeniculum vulgare essential oil and its main components; trans-anethole and fenchone; against R. annulatus. GC-MS analysis revealed that this oil contained 16 components representing 99.9% of the total identified compounds with E-anethole being the predominant component(64.29%), followed by fenchone (9.94%). The fennel oil and trans-anethole showed significant acaricidal activities. The LC50 of the fennel oil was attained at concentrations of 12.96% for adult ticks and 1.75% for tick larvae meanwhile the LC50 of trans-anethole was reached at concentrations of 2.36% for adult tick and 0.56% for tick larvae. On the contrary, fenchone showed no any significant adulticidal activities and its LC50 attained at a concentration of 9.11% for tick larvae. Regarding repellence activities, trans-anethole achieved 100% repellency at the concentration of 10% while fennel showed 86% repellency at the same concentration. Fenchone showed no repellency effect. Treatment of larvae with fennel, trans-anethole, and fenchone LC50 concentrations significantly inhibited the acetylcholinesterase activity. Meanwhile, glutathione s-transferase activity was significantly decreased in fennel treated larvae but no significant effect was found in the larvae of trans-anethole and fenchone groups. These results indicate that the acaricide effect of fennel oil may attributed to its high content of trans-anethole. This was supported by potent adulticidal, larvicidal, and repellency effects of trans-anethole against Rhipeciphalus annulatus tick and therefore it could be included in the list of acaricide of plant origin

Prevalence and antimicrobial sensitivity of Escherichia coli and Salmonella species in field cases of rabbit intestinal coccidiosis treated with prebiotic

This study aimed to investigate the effect of prebiotic treatment on E. coli and Salmonella species during natural intestinal coccidiosis in rabbits. The experiment was conducted on 45 selected farm rabbits of which 15 were coccidian free (Negative control; NC, group) and 30 were naturally coccidian infected. The infected animals were allocated into two equal groups including positive control (PC) and prebiotic treated (PT) that were orally treated with prebiotic for 8 successive days. Fecal oocyst count was assessed daily during the course of treatment. Meanwhile, the PC group had a significantly high oocyst count (21.67×103 ± 0.82 OPG), with a significant increase in the prevalence of E. coli and Salmonella (86.7 % and 46.7 %, respectively). Moreover, the NC group remained coccidian free and exhibited E. coli infection only with no detection of salmonella isolates. Findings of in-vitro susceptibility testing showed that E. coli isolates were highly resistant to most of the tested antimicrobials while Salmonella isolates showed variable degrees of resistance. In conclusion, the prebiotic treatment significantly reduced the prevalence of E. coli and Salmonella infections coexisted with intestinal coccidiosis in naturally infected rabbits

Prevalence of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in Upper Egypt

<p>Abstract</p> <p>Background</p> <p>Pseudoexfoliation (PXF) is a recognized risk factor for developing cataract, glaucoma and lens dislocation. PXF is also associated with increased risk of complications during cataract surgery due to poor mydriasis and zonular weakness. The aim of this study is to report the prevalence of pseudoexfoliation among Upper Egyptians attending the ophthalmology clinic of Assiut University Hospital.</p> <p>Methodology</p> <p>A retrospective, chart review study conducted in the period from February 2002 to August 2009. A total of 7738 patients aged 40 years or older attending the general ophthalmic clinics were included in this study. A detailed evaluation including ophthalmic and general history, slit lamp biomicroscopy, intraocular pressure measurement, gonioscopy and dilated eye examination were performed. Patients with pseudoexfoliative material on the anterior lens surface and ⁄ or the pupillary margin in either or both eyes were labeled as having PXF.</p> <p>Results</p> <p>Out of the 7738 patients included, three hundred twenty (4.14%) subjects had PXF. Mean age of PXF group was 68.15 years (SD 8.16, range 40-92 years). PXF was bilateral in 82.2% of cases. It was significantly associated with cataract, glaucoma and hearing loss. Of the PXF patients, 65% had cataract, 30.3% had glaucoma and 8.1% had hearing loss.</p> <p>Conclusion</p> <p>Pseudoexfoliation appears to be a common disorder in older individuals in Upper Egypt.</p

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Diversity of Parasitic Diarrhea Associated with <i>Buxtonella Sulcata</i> in Cattle and Buffalo Calves with Control of Buxtonellosis

The association between parasite isolates, including Buxtonella sulcata, in suckling and post-weaning calves and diarrhea was studied with the aim to control diarrhea caused by B. sulcata. A total of 1100 diarrheic fecal samples were collected from 609 suckling calves and 491 post-weaning calves with diarrhea. Salt floatation and modified Ziehl&#8722;Neelsen techniques were applied for the microscopic examination of the presence or absence of parasite eggs and oocysts/cysts. The microscopic findings revealed that 20.36% of the calves had parasitic diarrhea, with a prevalence rate of 19.54% in suckling calves and 21.38% in post-weaning calves. The most frequently detected parasites according to morphological characters were Eimeria species, Buxtonella sulcata, Toxocara vitulorum, Cryptosporidium species, and Moneizia species. In suckling calves, Eimeria species, B. sulcata, and T. vitulorum had the highest prevalence rates of infection, corresponding to about 37.14%, 32.86%, and 20.00%, respectively. However, in post-weaning calves, B. sulcata infection was more prevalent (30.15%) than infections with Eimeria species and T. vitulorum. The highest parasite score density was found in multiple infections with B. sulcata, Eimeria species, and T. vitulorum; however, the score density of B. sulcata when present alone in the fecal specimens was higher than in specimens co-infected with other parasites. The risk factors affecting the prevalence rate of parasitic diarrhea, such as sex, season, housing system, and feed stuff, are discussed. Concerning the treatment of diarrhea caused by B. sulcata in post-weaning cattle calves, 20 calves were divided into 4 equal groups. Group A was given sulphadimidine sodium (1.0 g/10 kg body weight) and metronidazole (500 mg/40 kg body weight); group B was treated with oxytetracycline hydrochloride (500 mg/45 Kg of body weight) and metronidazole (500 mg/40 kg body weight); group C was daily administered garlizine (allicin), 2 g/ L in drinking water; group D was the untreated control group. All medications were administered orally for four successive days. The results showed that the cyst count was significantly lower in the drug-treated groups, and the metronidazole + oxytetracycline hydrochloride and metronidazole + sulphadimidine combinations achieved 98.77% and 96.44% efficacy, respectively. Garlizine had 72.22% efficacy. Intriguingly, B. sulcata infection was associated with other parasitic infections, but B. sulcata mono-infection was the most common cause of diarrhea. Moreover, the combinations of oxytetracycline hydrochloride or sulphadimidine with metronidazole are recommended to control buxtonellosis in calves. Further studies are recommended to investigate the bacterial, viral, and fungal infections associated with B. sulcata infection

Biological control of Podosphaera xanthii the causal agent of squash powdery mildew disease by upregulation of defense-related enzymes

Abstract Squash (Cucurbita pepo L.), one of the most important vegetable crops for human nutrition all over the world, is infected by many diseases, particularly powdery mildew caused by Podosphaera xanthii (syn. Sphaerotheca fuliginea), which is considered the most serious disease causing yield losses. This research study was conducted to investigate the role of Bacillus subtilis, Bacillus chitinosporus, Bacillus pumilus, Bacillus megaterium, Bacillus polymexa, Trichoderma harzianum, and Trichoderma viridi on squash leaves infected with P. xanthii under laboratory and greenhouse conditions. Results indicated that all treatments significantly inhibited the conidial germination of P. xanthii than the control. A significant decrease in the disease symptoms, severity, and the area under disease progress curve (AUDPC) was registered in squash plants sprayed with the tested bio-agents, particularly B. subtilis, B. pumilus, and T. harzianum. The activity of defense-related enzymes, i.e., catalase (CAT), peroxidase (POX), and polyphenol oxidase (PPO), were significantly upregulated as results of most treatments. Light and scanning electron microscopic (SEM) investigation showed that the morphological shape of P. xanthii was abnormal and the pathogen growth was limited in bio-agent-treated plants compared to control plants that showed dramatic infection. Bio-agent treatments significantly increased growth and yield attributes of squash plants over control. Overall, the results showed possibility of using the tested bio-agents to control squash powdery mildew disease as an alternative to fungicides’ use that is harmful for human health and polluting the environment