Meta-inhibition of ocular and gastrointestinal dysfunctions by phenolic-rich fraction of Croton zambsicus leaves in a rat model exposed to chronic mixed metals.

PURPOSE: This study was aimed at investigating the protective effect of antioxidant-rich fraction of Croton zambsicus (C-ZAMB) leaves on ocular-gastrointestinal dysfunction in rats exposed to environmental mixed-metal (EOMABRSL). MATERIALS AND METHODS: The rats were divided into five (n = 10) groups. Group I designates the control which received 0.5 mL of distilled water. Group II and III received 0.5 mL of EOMABRSL for 98 days (non-withdrawal) and 70 days (withdrawal for 28 days), respectively. Group IV received 0.5 mL EOMABRSL for 70 days and 400 mg/kg C-ZAMB fraction for 28 days. Group V received 400 mg/kg C-ZAMB only for 28 days via oral route. RESULTS: Exposure of the animals to EOMARBSL for 98 days and 70 days significantly up-regulated the activities of ocular-gastrointestinal aldolase-reductase, α-amylase, α-glucosidase and eco-51-nucleotidase with corresponding depletion of lactate dehydrogenase activity. Furthermore, exposure to EOMABRSL significantly altered the antioxidant proteins with up-production of MDA content. Apparently, management with 400 mg/kg C-ZAMB fraction significantly inhibited the key markers linked with ocular-gastrointestinal disorders. CONCLUSION: Hence, this study underscores the biochemical mechanisms for managing ocular-gastrointestinal lesions by 400 mg/kg C-ZAMB fraction on exposure to mixture of environmental metals.

Ocular Effects of Sulfur Mustard and Therapeutic Approaches.

Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes, and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis, and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication, and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD), and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation, and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin ß4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin, and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. J. Cell. Biochem. 118: 3549-3560, 2017. © 2017 Wiley Periodicals, Inc.

Side effects of retinoid therapy on the quality of vision.

Retinoids are compounds chemically related to vitamin A, which are frequently used in dermatological practice (1). They are characterized by numerous mechanisms of action leading to normalization of keratinocyte proliferation and maturation. They have anti-seborrhoeic, immunomodulatory and anti-inflammatory effects (1, 2). A number of side effects to retinoid treatment have been recorded; one group of such side effects relates to eyes and vision. Dry eye syndrome and blepharoconjunctivitis are the most common side effects, appearing in 20-50 % of patients treated with retinoids. They often contribute to the occurrence of other side-effects such as eye discomfort and contact lens intolerance. Due to the widespread use in clinical practice, the adverse effects, including ocular side effects, should be studied. To confirm the variety of adverse effects of retinoids, several case reports of rare side-effects are presented.

Ocular changes induced by drugs commonly used in dermatology.

The use of many drugs in dermatologic diseases may cause ocular side effects. Some may regress after discontinuation of the therapy, but others persist or progress even after the cessation of treatment. This review presents four groups of commonly prescribed drugs-antimalarial medicines, glucocorticoids, retinoids, and psoralens + ultraviolet A (UVA) therapy-and discusses their possible ocular side effects. The most significant complication of antimalarial drugs is retinopathy with the risk of permanent visual impairment. There are different recommendations for screening for this drug-related retinopathy. The most important ocular manifestations of steroid management are irreversible optic nerve damage in "steroid responders" (steroid glaucoma) and cataract. Some other side effects may disappear after discontinuation of the therapy. Retinoid-induced ocular side effects include ocular surface disease as well as retinal dysfunction. It is recommended to modify the therapy when night blindness occurs or after the decrease of color vision. Protective eyewear is sufficient to avoid ocular surface problems during psoralen + UVA therapy. The knowledge of screening schemes and closer cooperation between physicians may decrease the risk of serious or irreversible ocular side effects.

The effect of thiamine pyrophosphate on ethambutol-induced ocular toxicity.

CONTEXT: Ethambutol-induced retinal oxidative damage in patients with tuberculosis is still not being adequately treated. The protective effect of thiamine pyrophosphate against oxidative damage in some tissues has been reported, but no information on the protective effects of thiamine pyrophosphate against ethambutol-induced oxidative retinal damage has been found in the medical literature. OBJECTIVE: The objective is to investigate whether thiamine pyrophosphate has a protective effect against oxidative retinal damage in rats induced by ethambutol. MATERIALS AND METHODS: Experimental animals divided into four groups (n = 10): the healthy group (HG), the ethambutol control group (EMB), thiamine + ethambutol group (Thi-EMB) and thiamine pyrophosphate + ethambutol group (TPP-EMB). The rats in the TPP-EMB and Thi-EMB groups were administered thiamine pyrophosphate and thiamine, respectively, at doses of 20 mg/kg intraperitoneally. Distilled water was administered intraperitoneally to the HG and the EMB groups as a solvent in the same volumes. One hour after drug injection, 30 mg/kg ethambutol was administered via an oral gavage to the TPP-EMB, Thi-EMB and EMB groups. This procedure was repeated once a day for 90 days. At the end of this period, all rats were euthanized under high-dose thiopental sodium anesthesia, and biochemical and histopathological investigations of the retinal tissue were performed. RESULTS: Malondialdehyde (MDA) and DNA damage product 8-hydroxyguanine levels were significantly lower in the retinal tissue of TPP-EMB and HG groups compared to those of the Thi-EMB and EMB groups, and total glutathione (tGSH) was also found to be higher. In addition, severe retinal tissue vascularization, edema and loss of ganglion cells were observed in the Thi-EMB and EMB groups, whereas histopathological findings for the TPP-EMB group were observed to be close to normal. DISCUSSION AND CONCLUSION: These findings suggest that thiamine pyrophosphate protects retinal tissues from ethambutol-induced oxidative damage, and thiamine does not. This positive effect of thiamine pyrophosphate may be useful in the prevention of ocular toxicity that occurs during ethambutol use.

Clinicopathological effects of pepper (oleoresin capsicum) spray.

OBJECTIVES: Pepper (oleoresin capsicum) spray is one of the most common riot-control measures used today. Although not lethal, exposure of pepper spray can cause injury to different organ systems. This review aimed to summarise the major clinicopathological effects of pepper spray in humans. DATA SOURCES: MEDLINE, EMBASE database, and Cochrane Database of Systematic Reviews were used to search for terms associated with the clinicopathological effects of pepper spray in humans and those describing the pathophysiology of capsaicin. A phone interview with two individuals recently exposed to pepper spray was also conducted to establish clinical symptoms. STUDY SELECTION: Major key words used for the MEDLINE search were "pepper spray", "OC spray", "oleoresin capsicum"; and other key words as "riot control agents", "capsaicin", and "capsaicinoid". We then combined the key words "capsaicin" and "capsaicinoid" with the major key words to narrow down the number of articles. A search with other databases including EMBASE and Cochrane Database of Systematic Reviews was also conducted with the above phrases to identify any additional related articles. DATA EXTRACTION: All article searches were confined to human study. The bibliography of articles was screened for additional relevant studies including non-indexed reports, and information from these was also recorded. Non-English articles were included in the search. DATA SYNTHESIS: Fifteen articles were considered relevant. Oleoresin capsicum causes almost instantaneous irritative symptoms to the skin, eyes, and respiratory system. Dermatological effects include a burning sensation, erythema, and hyperalgesia. Ophthalmic effects involve blepharospasm, conjunctivitis, peri-orbital oedema, and corneal pathology. Following inhalation, a stinging or burning sensation can be felt in the nose with sore throat, chest tightness, or dyspnoea. The major pathophysiology is neurogenic inflammation caused by capsaicinoid in the pepper spray. There is no antidote for oleoresin capsicum. Treatment consists of thorough decontamination, symptom-directed supportive measures, and early detection and treatment of systemic toxicity. Decontamination should be carefully carried out to avoid contamination of the surrounding skin and clothing. CONCLUSION: Pepper (oleoresin capsicum) spray is an effective riot-control agent and does not cause life-threatening clinical effects in the majority of exposed individuals. Early decontamination minimises the irritant effects.

[Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations]. / Ophthalmologische Komplikationen und Lokalanästhesie. Pathophysiologie und Formen der Augenkomplikationen nach intraoraler zahnärztlicher Lokalanästhesie und klinische Empfehlungen.

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

Ophthalmic complications of targeted cancer therapy and recently recognized ophthalmic complications of traditional chemotherapy.

As our understanding of cancer pathophysiology has increased, so have the number of targeted therapeutic agents available. By targeting specific molecules involved in tumorigenesis, targeted therapeutic agents offer the potential for significant efficacy against tumor cells while minimizing the adverse effects. We highlight the recently recognized ophthalmic complications of targeted cancer therapy, as well as recently recognized complications of traditional chemotherapeutic agents.

Ophthalmologic complications after intraoral local anesthesia.

INTRODUCTION: The first ophthalmologic complication in conjunction with a dental anesthesia was reported in 1936. The objective of the present study was a detailed analysis of case reports about that topic. MATERIAL AND METHODS: After conducting a literature search in PubMed this study analyzed 108 ophthalmologic complications following intraoral local anesthesia in 65 case reports with respect to patient-, anesthesia-, and complication- related factors. RESULTS: The mean age of the patients was 33.8 years and females predominated (72.3%). The most commonly reported complication was diplopia (39.8%), mostly resulting from paralysis of the lateral rectus muscle. Other relatively frequent complications included ptosis (16.7%), mydriasis (14.8%) and amaurosis (13%). Ophthalmologic complications were mainly associated with block anesthesia of the inferior alveolar nerve (45.8%) or the posterior superior alveolar nerve (40.3%). Typically, the ophthalmologic complications in conjunction with intraoral local anesthesia had an immediate to short onset, and disappeared as the anesthesia subsided. DISCUSSION AND CONCLUSION: The increased number of ophthalmologic complications after intraoral local anesthesia in females may suggest a gender effect. Double vision (diplopia) is the most frequently described complication, which is usually completely reversible like the other reported ophthalmologic complications.

[Long-term complications of sulfur mustard exposure: a therapeutic update].

Sulfur mustard (SM) is an alkylating chemical warfare agent with high military significance due to its high toxicity, resistance and availability. SM was widely used in military conflicts, the last being the Iran-Iraq war with more than 100,000 Iranians exposed, one-third of whom are still suffering from late effects. The intensity of the delayed complications correlates to the extent, the area and the route of exposure. The clinical manifestations most commonly involve respiratory, ocular and dermal effects. Respiratory complications include dyspnea, cough and expectorations and various obstructive and restrictive lung diseases. Dermal complications are itching, burning sensation, blisters, dry skin, dermatitis and pigmentary changes. Ocular complications include photophobia, red eye, tearing, corneal ulcers and blindness. Although the picture remains incomplete the major mechanisms responsible for the clinical and pathological effects of SM are: DNA alkylation and cross-linking, protein modification and membrane damage in addition to induction of inflammatory mediators in the target tissues causing extensive necrosis, apoptosis and loss of tissue structure. The current report reviews long-term complications of SM exposure, focusing on new treatments tested in clinical trials conducted on humans. Such treatments include: N-acetyl cysteine, bronchodilators, corticosteroids, Interferon-gamma, furosemide and morphine for the respiratory complications. Ocular complications may entail: Invasive procedures treating corneal complication, limbal ischemia and stem cell deficiency. Treatment for dermatological complications include: anti-depressants, pimercrolimus, Unna's boot, capsaicin, phenol and menthol, Aloe vera and olive oil, curcumin and Interferon-gamma.

Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

OBJECTIVE: To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. METHODS: Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. RESULTS: While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. DISCUSSION: Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

Safety evaluation of a lipase enzyme (BD29241 Palmitase) preparation, expressed in Pseudomonas fluorescens, intended for removing palmitic acid from triacylglycerol.

The lipase enzyme, BD29241 Palmitase, can be used as a processing aid for removing palmitic acid from triacylglycerol in the production of refined oil. This enzyme was produced from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested in acute, inhalation, and subchronic toxicity studies. In addition, this enzyme was also tested for its potential to induce genotoxicity. Dosages of the test article preparation ranged from 5000µg/plate for in vitro toxicity studies to 2000mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000mg/kg/day) resulted in a safety margin of 2.442×10(3) based on a conservative estimate of the total human consumption of BD29241 Palmitase of 0.819mg/kg/day. There was no toxicity reported for any of these studies including additional safety studies. A review of the literature indicates that P. fluorescens fulfills recognized safety criteria pertinent to microbial production strains used in the manufacture of food enzyme preparations. The results of the toxicity studies presented herein attest to the safety of BD29241 Palmitase for its above-stated intended use.

The duration of acute health problems in people involved with the cleanup operation of the Hebei Spirit oil spill.

The authors investigated the duration of health problems of people involved with cleanup efforts for the Hebei Spirit oil spill, which occurred in December 2007 in Taean County, South Korea. The study identified risk factors correlated with the continuation of symptoms. Approximately one year after the accident, 442 people who had participated in the cleanup operation were examined. Data regarding demographic information, risk factors, and the continuation and duration of any symptoms were obtained. Eye symptoms (9.7 months), headaches (8.4 months), skin symptoms (8.3 months), and neurovestibular symptoms (6.9 months) had a relatively longer duration than did back pain (1.8 months) or respiratory symptoms (2.1 months). In particular, the remission of headaches had a negative correlation with female gender (HR 0.57, 0.34-0.95, 95% CI), and remission of eye symptoms had a negative correlation with the total hours of daily participation in the cleanup operation (HR 0.24, 0.06-0.95, 95% CI).

Ocular adverse effects of systemic treatment with isotretinoin.

OBJECTIVE: To examine whether isotretinoin therapy could result in deleterious ocular effects, as previously described in case report studies. DESIGN: Retrospective cohort study. SETTING: The study was conducted using the electronic medical databases of a large health maintenance organization in Israel. PATIENTS: The study population consisted of 14 682 adolescents and young adults who were new users of isotretinoin for acne and 2 age- and sex-matched comparison groups (isotretinoin-naive patients with acne and acne-free patients). MAIN OUTCOME MEASURES: Ocular adverse effects (AEs) or purchases of ophthalmic medications within 1 year after the first dispensed isotretinoin prescription. RESULTS: In total, 13.8% of the isotretinoin group experienced ocular AEs vs 9.6% of the isotretinoin-naive group and 7.1% of the acne-free group. During a 1-year follow-up period, the isotretinoin group had significantly higher risk for any ocular AEs (hazard ratio, 1.70; P.001) compared with the acne-free group. No such increased risk was observed for the isotretinoin-naive group. The isotretinoin group had higher relative risks for inflammatory and structural AEs. CONCLUSION: Isotretinoin use may be associated with short-term ocular events, especially conjunctivitis, underscoring the importance of educating patients and caregivers about these potentially important AEs of the therapy.

Occular complications following dental local anesthesia

Objective: To determine the frequency of app earance and the factors most comm only associated with ocular complicationsfollowing dental local anesthesia, also establishing the location and typ e of anesthesia used.Study Design: An indexed search in the Pubmed and Comp ludoc databases was carried out with the keywords“oral anesthesia”, “ocular”, “ophthalmologic”, “damage”, “comp lications”, “injection”. We established a limitationthat the literature had to have been published after the year 1970. A total of 19 articles were obtained, forming atotal samp le of 37 patients. The patient’s sex, age, nerve anesthetized, typ e of anesthetic used, ophthalmologicalcomp lication present, recovery time, treatment and side effects were analyzed.Results: There is a higher involvement of females (77%). The average age was 34.2 years. There was no preferencefor an anesthetic technique. Diplopia was the most comm on comp lication (65%), which coincides with the datafrom other authors. Almost all of the comp lications were of a temp orary nature, with an average recovery time of68 minutes.Conclusions: This is one of the few studies of its kind in dental literature, it thus being difficult to make preciseconclusions. Ophthalmological comp lications are seldom a problem, diplopia being the most comm on amongthem. The authors app ear to indicate an intravascular injection of the anesthetic as the cause of the problem, andtherefore, it should be avoided in order to prevent accidents at the ocular level (AU)

[Irritant stability of raphides and tubers from Pinellia ternate].

OBJECTIVE: To investigate the irritation stability of raphides from Pinellia ternata and the contribution of raphides proteins on irritation. METHODS: The irritation of raphides and tubers from P. ternata treated with different solvents or protease digestion were evaluated by the Draize test. The shape and appearance of raphides treated with immersion in different solvents were showed by scanning electron microscopy, and protein bands from raphides before and after protease digestion were showed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The raphides gradually lost the irritation when immersed in methanol and ethanol, while scanning electron micrograph showed the fragility of the methanol and ethanol treated raphides. The crude tubers of P. ternata immersed in 75% solution of ethanol also lost the acridity. When treated with protease digestion, raphides lost the irritation as well as the many protein bands on the SDS-PAGE gel gradually disappeared. CONCLUSION: Protein of the raphides could be involved in the raphides irritation.

Subchronic (13-week) oral toxicity study in rats with fungal chitin-glucan from Aspergillus niger.

Chitin-glucan is an insoluble biopolymer, composed of chitin and beta-(1,3)-D-glucan, that is a component of the fungal cell wall. This study was conducted to assess the safety of chitin-glucan from the mycelium of Aspergillus niger (Artinia brand) for use as dietary supplement and food ingredient. Chitin-glucan was fed to Wistar rats (20/sex/group) at dietary levels of 0, 1, 5 and 10% for 13 weeks. Clinical and neurobehavioural observations, growth, feed and water consumption, ophthalmoscopy, haematology, clinical chemistry, urinalysis, organ weights, necropsy and histopathological examination revealed no adverse effects of chitin-glucan. Rats fed chitin-glucan at 10% consumed more feed than controls, probably due to lower energy density of their diet. Water intake was increased slightly at all dose levels. These changes were not toxicologically significant. Full and empty caecum weights were increased in mid-dose males and high-dose males and females. This caecal enlargement was a physiological response to the consumption of a high amount of poorly digestible carbohydrate and considered of no toxicological concern. In conclusion, feeding chitin-glucan at dietary levels up to 10% for 13 weeks was tolerated without any signs of toxicity. This level corresponded to 6.6 and 7.0 g chitin-glucan/kg body weight/day in male and female rats, respectively.

28 Days repeated oral dose toxicity test of aqueous extracts of mahwangyounpae-tang, a polyherbal formula.

Mahwangyounpae-tang (MT), consisting of 22 types of herbal extracts has been used for thousands of years in Korean traditional medicine for the oral treatment of respiratory diseases including asthma. As part of a safety evaluation of MT extract for use in asthma, the 28 day repeat oral dose toxicity of an aqueous MT extract was evaluated at 800, 400 and 200mg/kg per day dose levels. The results showed that no significant toxicological changes were observed when 200 and 400mg/kg per day of MT extract was administered to rats. But when the dose was increased to 800 mg/kg per day, increases of body weights, food consumptions, and heart and kidney weights were observed with hypertrophy of heart and tubular necrosis of kidney. Besides this, no other signs of toxicity were observed. Based on these results, it can be concluded that the no observed adverse effect level of MT extract is 400mg/kg per day. Therefore, the use of MT is expected to be safe because 30 mg/kg was shown to be pharmacologically effective in mice and the high dose heart and kidney findings are not considered to represent any safety concern for humans.