Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.

Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.

The pathology of lethal exposure to the Riot Control Agents: towards a forensics-based methodology for determining misuse.

The aim of this is to review deaths associated with the use of Riot Control Agents (RCAs) and to assess how the presenting pathologies is such cases may better inform cause of death conclusions upon autopsy. We also sought to present which additional steps should be added to the Minnesota protocol and the European harmonization of medico-legal autopsy rules in suspected cases of deaths associated with the use of RCAs. We included 10 lethal cases in our study. In three cases, RCAs were found to be the sole cause of death, in three cases RCAs were ruled a secondary cause of death due asphyxia or asthma subsequent to exposure to RCAs and in four cases RCAs were contributory factors to death. In three cases the responsible agents were identified as Chloroacetophenone (CN), Chlorobenzylidene malononitrile (CS) and Oleoresin capsicum (OC) and in the remaining 7 cases, the agent was OC alone. As there are no specific findings in suspected cases of death associated with RCA use, establishing cause of death and whether RCAs are the sole cause or only a contributory factor will be based on the elimination of other possible causes of death. For this reason, a specifically structured autopsy is essential. This specifically structured autopsy should contain basic principles of the Minnesota Protocol and the European harmonization of medico-legal autopsy rules with the following additional steps taken: examination of clothing, eyes, and skin; examination of pharyngeal, tracheobronchial, and eusophegeal mucosas; and a thorough recording of the steps taken by the party conducting the arrest, including other possible causes of in-custody death, as well as a detailed medical history of the deceased.

Riot control agents: the tear gases CN, CS and OC-a medical review.

INTRODUCTION: 2-Chloroacetophenone (CN), o-chlorobenzylidene malonitrile (CS) and oleoresin capsicum (OC) are common riot control agents. While serious systemic effects are uncommon, exposure to high concentrations may lead to severe complications and even death. The aim of this narrative review is to summarise all main aspects of the riot control agents CN, CS and OC toxicology, including mechanisms of toxicity, clinical features and management. METHODS: OVID MEDLINE and ISI Web of Science were searched for terms associated with CN, CS and OC toxicity in humans and those describing the mechanism of action, clinical features and treatment protocols. RESULTS: CN, CS and OC are effective lacrimating agents; evidence for toxicity, as measured by the threshold for irritation, is greatest for CN, followed by CS and OC. Typically, ocular and respiratory tract irritation occurs within 20-60 s of exposure. Ocular effects involve blepharospasm, photophobia, conjunctivitis and periorbital oedema. Following inhalation, effects may include a stinging or burning sensation in the nose, tight chest, sore throat, coughing, dyspnoea and difficulty breathing. Dermal outcomes are variable, more severe for CN and include dermal irritation, bulla formation and subcutaneous oedema. Removal from the contaminated area and fresh air is a priority. There is no antidote; treatment consists of thorough decontamination and symptom-directed supportive care. Ocular exposure requires thorough eye decontamination, an eye exam and appropriate pain management. Monitoring and support of respiratory function is important in patients with significant respiratory symptoms. Standard treatment protocols may be required with patients with pre-existing respiratory conditions. Dermal exposures may require systemic steroids for patients who develop delayed contact dermatitis. CONCLUSIONS: CN, CS and OC are effective riot control agents. In the majority of exposures, significant clinical effects are not anticipated. The irritant effects can be minimised both by rapid evacuation from sites of exposure, decontamination and appropriate supportive care.

Effect of food seasoning spices mixture on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats.

High fructose feeding in normal rats induces insulin resistance and also facilitates oxidative damage. The present study examines the effects of a spices mixture (SM) on oxidative stress markers and antioxidant potential in tissues of high fructose-fed insulin-resistant rats. Male Wistar rats received a semisynthetic diet containing either 60% fructose or 60% starch. SM administration at three different doses (10, 30, and 50 mg/day per rat) was initiated orally 15 days later and continued for the next 30 days. After the total experimental period of 45 days, peroxidation of lipids and antioxidant status in liver and kidney were quantified. Fructose-treated rats showed increased levels of peroxidation indices such as thiobarbituric acid-reactive substances and lipid hydroperoxides in tissues. The condition was associated with an inadequate antioxidant system. Administration of SM along with fructose diet reduced the levels of peroxidation markers in tissues and improved the antioxidant status. The positive effect of SM on the oxidant-antioxidant balance could be attributed to the active constituents of the different spices present in the mixture.

Free radical scavenging activity, metal chelation and antioxidant power of some of the Indian spices.

Food constituents are the major source of various phytochemicals and micronutrients. The importance of these dietary constituents has been stressed in recent years due to their antioxidant and anticarcinogenic potential. Spices used in Indian foods such as cloves (Syzygium aromaticum), licorice (Glycyrrhiza glabra), mace (aril of Myristica fragans), and greater cardamom (Amomum subulatum) were tested for their antioxidant properties in vitro. The metal chelating activity, bleomycin dependent DNA oxidation, diphenyl-p-picryl hydrazyl (DPPH) radical scavenging activity and the ferric reducing /antioxidant power (FRAP) were measured in rat liver homogenate in presence of spices. Metal chelating activity was significantly high with all the spice extracts except mace. The spices due to higher reducing potential (in presence of bleomycin-FeCl_{3}) showed increased DNA oxidation. Cloves showed the highest DPPH radical scavenging activity, followed by licorice, mace and cardamom. FRAP values for cloves were also the highest, while other spices showed comparatively lesser FRAP values. The results show that the spices tested are strong antioxidants and may have beneficial effects on human health.

An evaluation of the relative potential public health concern for the self-defense spray active ingredients oleoresin capsicum, o-chlorobenzylidene malononitrile, and 2-chloroacetophenone.

In 1996, the New York State Department of Health was charged by the State Legislature to develop regulations regarding the types of self-defense spray devices which could lawfully be purchased, possessed, and used in New York State. Prior to this legislation, sale or possession of self-defense spray devices in New York State was illegal. The Department of Health used existing data to evaluate three commonly used self-defense spray active ingredients (oleoresin capsicum, o-chlorobenzylidene malononitrile, and 2-chloroacetophenone) with respect to their relative toxicity and their involvement in accidental poisonings. Based on the balance of the available information, the Department of Health determined that oleoresin capsicum posed a lower public health concern than o-chlorobenzylidene malononitrile or 2-chloroacetophenone, and developed a rule that specifies oleoresin capsicum as the only active ingredient to be used in self-defense sprays for sale and use in New York State.

Personal aerosol protection devices: caring for victims of exposure.

The increased incidence of violence in our society has led to a concern for personal safety. For self-protection, many individuals are turning to personal aerosol protection devices (PAPDs), which are readily accessible to the general public. The greater use and misuse of these noxious chemicals has led to an increase in injuries associated with exposure. Health care providers need to be aware of the modes of action of PAPDs, the presenting exposure symptoms, first aid measures, and decontamination procedures of the environment and the victim's belongings. This article provides a thorough discussion of PAPDs and will assist the clinician in delivering primary care and health education to victims of PAPD exposures.

Transmammary modulation of xenobiotic metabolizing enzymes in liver of mouse pups by mace (Myristica fragrans Houtt.).

The present study examines the possible transfer of the active principle(s) of mace (aril of the plant Myristica fragrans) through the transmammary route and its ability to modulate hepatic xenobiotic metabolizing enzymes in the F1 progeny of mice. An aqueous suspension of mace at the dose levels of 0.025 or 0.1 g/animal/day was administered by oral gavage to dams from day 1 of lactation and continued daily for 14 or 21 days. Dams receiving mace treatment and their F1 pups showed significantly elevated hepatic sulfhydryl content, glutathione S-transferase and glutathione reductase activities and cytochrome b5 content. Hepatic cytochrome P450 content decreased in dams (P < 0.05) receiving the lower mace dose for 21 days and the F1 pups (P < 0.001), but increased in dams receiving the higher dose for both time periods (P < 0.001) and the lower dose for 14 days (P < 0.05). Only the 14-day-old pups of dams receiving either mace dose showed significantly elevated (P < 0.001) levels of hepatic glutathione peroxidase.

Microbial degradation of chlorinated acetophenones.

A defined mixed culture, consisting of an Arthrobacter sp. and a Micrococcus sp. and able to grow with 4-chloroacetophenone as a sole source of carbon and energy, was isolated. 4-Chlorophenyl acetate, 4-chlorophenol, and 4-chlorocatechol were identified as metabolites through comparison of retention times and UV spectra with those of standard substances. The proposed pathway was further confirmed by investigation of enzymes. The roles of the two collaborating strains were studied by growth experiments and on the level of enzymes. If transient accumulation of 4-chlorophenol was avoided either by the use of phenol-absorbing substances or by careful supplement of 4-chloroacetophenone, the Arthrobacter sp. was able to grow as a pure culture with 4-chloroacetophenone as a sole source of carbon and energy. Several mono-, di-, and trichlorinated acetophenones were mineralized by the Arthrobacter sp.