Safety assessment of Streptococcus salivarius M18 a probiotic for oral health.

The development of probiotics targeting non-intestinal body sites continues to generate interest amongst researchers, biotech companies and consumers alike. A key consideration for any bacterial strain to be developed into a probiotic is a robust assessment of its safety profile. Streptococcus salivarius strain M18 was originally isolated from a healthy adult and evaluated for its probiotic capabilities targeted to dental and oral health applications. This publication presents the safety characterisation of strain M18. Application of a diverse range of techniques showed that strain M18 can be specifically distinguished from other S. salivarius using a variety of molecular and phenotypic methodologies and that it lacks any relevant antibiotic resistance or virulence determinants. Direct comparison of the strain M18 safety profile with that of the prototype S. salivarius probiotic, S. salivarius strain K12, supports the proposition that strain M18 is indeed safe for probiotic application in humans.

Safety assessment of the post-harvest treatment of button mushrooms (Agaricus bisporus) using ultraviolet light.

Wild mushrooms are an excellent source of vitamin D. The presence of vitamin D in mushrooms is attributed to sunlight exposure, which catalyzes the conversion of fungal ergosterol to vitamin D2 via a series of photochemical/thermal reactions. Mushroom growers now incorporate UV light treatments during processing to produce mushrooms with levels of vitamin D that compare to those in wild mushrooms. Presented herein is a comprehensive review of information relevant to the safety of introducing vitamin D mushrooms, produced using UV light technologies, to the food supply. Historical reference to the use of UV light for production of vitamin D is discussed, and studies evaluating the nutritional value and safety of vitamin D mushrooms are reviewed. Traditional safety evaluation practices for food additives are not applicable to whole foods; therefore, the application of substantial equivalence and history-of-safe-use is presented. It was demonstrated that vitamin D in mushrooms, produced using UV light technologies, are equivalent to vitamin D in mushrooms exposed to sunlight, and that UV light has a long-history of safe use for production of vitamin D in food. Vitamin D mushrooms produced using UV light technologies were therefore considered safe and suitable for introduction to the marketplace.

Subchronic toxicity evaluation of potato protein isolates.

The protein content of potatoes has a high nutritional value on par with eggs and soybeans. As a result, processed potato protein isolates may have commercial value for addition to other food products to increase protein content. A manufacturing process has been developed to produce total potato (TP), as well as low (LMW) and high molecular (HMW) weight, protein isolates as food ingredients. To assess the safety of these isolates, groups of 10 Wistar rats/sex were administered dietary admixtures containing 15% HMW, 7.5% LMW or 15% TP protein isolates for a period of 90days. There was no effect of treatment on clinical signs, mortality, body weight and body weight gain. No biologically significant changes occurred in hematological and clinical chemistry parameters. No statistically significant changes in organ weights were recorded. Histopathological analyses revealed no clear, treatment-related changes. A slight increase in the incidence, but not severity, of vacuolation of the zona fasciculate of the adrenal gland was noted in males of the 15% HMW and 7.5% LMW groups. The finding was not considered adverse or ascribed any toxicological significance. Overall, HMW, LMW, and TP protein isolates were well-tolerated and without adverse effect. These data support the safety of potato protein isolates.

Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study.

Streptococcus salivarius is naturally a predominant member of the human oropharynx and the commercial probiotic strain K12 has been consumed for more than a decade. The present study examines the health responses of human volunteers to oral ingestion of high doses of S. salivarius K12. A randomized group of 53 subjects received a dose of 1 × 10(10)cfu S. salivarius K12 (N=25) or placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine and saliva samples were collected at baseline and following treatment and analyzed, while the oral and gastrointestinal tolerance of the subjects to the dosing regimen was determined by use of questionnaires. Adverse events (AE)s were recorded for both groups. No statistically significant differences between the probiotic and placebo treated groups were detected in either the blood clinical chemistry or hematology results (P>0.05). The questionnaire responses of the subjects indicated that both treatments were well tolerated. The frequency and intensity of AEs was similar in the two groups. This data demonstrates that the daily ingestion of S. salivarius K12 over a 28-day period does not adversely affect the human host and supports the safety of its oral delivery in a food-based carrier.

A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals.

Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or 'pre-diabetes'. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog , and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or 'pre-diabetes', GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance.

Genotoxicity and subchronic toxicity evaluation of Active Hexose Correlated Compound (AHCC).

Active Hexose Correlated Compound (AHCC), a mushroom extract rich in α-1,4 linked glucans, is associated with immunostimulatory effects. AHCC is used in Japan as a dietary supplement to boost immune function and it also is purported to improve the symptoms of cancer and liver disease patients. A series of toxicological studies were conducted on a freeze dried preparation of AHCC (AHCC-FD) to further develop the body of evidence supporting the safety of this ingredient. AHCC-FD was not mutagenic to Salmonella typhimurium and did not exhibit clastogenicity in a mouse micronucleus assay. In a 90-day study, Sprague-Dawley rats were administered 1000, 3000, or 6000 mg/kg body weight/day by gavage. No changes attributable to AHCC-FD treatment were observed in overall condition, body weight, food consumption, ophthalmology findings, hematology and clinical chemistry parameters, and absolute and relative organ weights. Changes in urinary pH values observed in high-dose animals and mid-dose females were considered physiological rather than adverse effects given the acidic nature of AHCC-FD. Urinary protein also was increased in the same dose groups. As this finding was associated with decreased urinary pH and no evidence of kidney dysfunction was observed, it was considered of no toxicological significance. Histopathological changes related to AHCC-FD administration were observed in the limiting ridge of the stomach and in the liver of the high-dose group. The NOAEL was considered to be 3000 mg/kg body weight/day.

Toxicological assessment of a particulate yeast (1,3/1,6)-beta-D-glucan in rats.

This study investigates the toxicity of WGP 3-6, a yeast-derived beta-glucan ingredient, during single-dose acute and sub-chronic toxicity studies in rats. For the acute study, Fisher-344 rats were administered WGP 3-6 via gavage at a dose of 2000 mg/kg body weight, and any evidence of toxicity was monitored over a 14-day period. WGP 3-6 was well tolerated, indicating that the LD(50) value is greater than 2000 mg/kg body weight. For the sub-chronic study, Fisher-344 rats (10/sex/group) were randomly allocated to receive daily gavage treatment with WGP 3-6 at doses of 0, 2, 33.3, or 100 mg/kg body weight. Control and high-dose satellite recovery groups of each sex also were included. Full toxicological monitoring and endpoint investigations were performed throughout and upon completion of the study. No negative effects on animal weights or food consumption attributable to WGP 3-6 were evident at any dose. In addition, no mortality, clinical pathology, functional/behavioral, microscopic, or gross observations indicating toxicity were observed. Sporadic changes in some biochemical and hematological parameters were observed; however, since the effects were within the physiological ranges in historical controls, were not dose-responsive, or were not observed in both sexes, they were determined to be of no toxicological significance. In conclusion, no adverse or toxic effects were observed after subchronic oral administration of 2, 33.3, or 100mg/kg body weight/day of WGP 3-6 in Fisher-344 rats, and therefore, a no observed adverse effect level (NOAEL) of 100 mg/kg body weight/day, the highest dose tested, was determined.

Metacarpal and phalangeal fractures.

Metacarpal and phalangeal fractures are common presenting injuries in many emergency departments. The emergency physician should become skilled at properly evaluating and initiating appropriate management and follow-up for these injuries when they occur. Failure to properly do so may result in permanent disability.

Emergency tracheotomy in patients with massive neck swelling.

Immediate control of the airway in a patient with massive neck swelling caused by cervical or maxillofacial trauma is often difficult. A modified new technique, discussed in this article, has been developed based on anatomic principles for the performance of a modified tracheotomy in these patients.

Logistics of medical care in rural Afghanistan.

The logistics of maintaining and supplying underground clinics located in war-torn rural Afghanistan are presented. Medical supplies are transported by pack animals over mountainous terrain, and must be specially packaged for the rigorous journey. Twenty percent of supplies are lost en route due to attacks or accidents. Medical and surgical equipment, some of which had to be specially designed, must be lightweight and durable. The system of monitoring clinic efficacy is also discussed.

Surgical theatre in rural Afghanistan.

We discuss the establishment of underground surgical theatres in resistance-held, rural Afghanistan by the IMC. The limitations of working in facilities without electricity or modern surgical equipment or even adequate suction are discussed, and the methods we have implemented to deal with these limitations are presented.

Surgical training model for advanced emergency medics in Afghanistan.

A surgical training model developed and implemented by the IMC for the training of advanced surgically capable medics operating in resistance-held rural Afghanistan is presented. Existing training programs for medics and midlevel health care workers are discussed, but these offer little or no surgical training and depend on a tiered system of referrals that is not possible in resistance-held Afghanistan. Details of the medics' training, enabling them to diagnose and treat 75% of war-related injuries in the rural population, are presented, as is the rationale for development of the model, based on data from other conflicts.

Sterilization techniques in underground surgical units in Afghanistan.

Sterilization equipment and techniques available to forward surgical units in modern conflicts past and present are sophisticated and generally taken for granted. Underground surgical units operating in rural Afghanistan must function without electricity or petroleum-powered generators and, with few exceptions, are unable to use sterilization equipment that produces intense heat for prolonged periods. We discuss the equipment and techniques developed for use by the IMC to sterilize surgical instruments, gowns, gloves, rubber goods, and sutures in the 42 clinics operating in resistance-held Afghanistan. These techniques may have application to other similar primitive conditions.

Moisture-vapour-permeable film as an outpatient burn dressing.

This study compares a moisture-vapour-permeable film (MVPF) with silver sulphadiazine in a randomized prospective manner for the treatment of outpatient burns. The two treatment groups were closely matched in age, sex, per cent of BSA burned, and in burn severity and locations. The MVPF group demonstrated a 39.0 per cent greater reduction in pain after application of the dressing over the silver sulphadiazine group. Patients in the MVPF film group also reported significantly less difficulty in wound care and in dressing interference with their daily functions. The clinical infection rate and time to healing were similar in both groups. In the management of outpatient burns, MVPF was found to be superior to silver sulphadiazine.

Cephalic vein cutdown at the wrist: comparison to the standard saphenous vein ankle cutdown.

We first developed a technique for cutdown of the cephalic vein at the wrist. We then conducted a prospective cross-over cadaver study comparing the ability of medical students to perform this technique with that of the standard saphenous vein cutdown at the ankle. All students had a previous course in anatomy but had never performed a cutdown. Before testing, the students were given written material and a ten-minute lecture describing both approaches. Seventeen students performed 34 cutdowns; nine students attempted the cephalic cutdown followed by the saphenous cutdown; the remaining eight used the reverse order. The mean time (+/- SD) to isolation of the cephalic vein was 85 +/- 70 seconds; for the saphenous vein, mean time was 70 +/- 89 seconds (P = NS). There was one failure (inability to isolate the vein within five minutes) in 17 attempts at the cephalic vein and two failures in 17 attempts at the saphenous (P = NS). There were no complications (nerve, artery, or tendon injury) with either technique. The mean external vein diameter (+/- SD) of the cephalic vein and the saphenous vein were 3.2 +/- 1.0 mm and 3.6 +/- 0.7 mm, respectively (P = NS). We conclude that relatively inexperienced providers can learn to perform the cephalic vein cutdown at the wrist on fresh cadavers with similar speed and success as that for the saphenous vein cutdown at the ankle. Cutdown at this site may provide a useful alternative to the saphenous cutdown in certain clinical situations.

Subungual hematoma: association with occult laceration requiring repair.

Subungual hematomas are one of the most common injuries involving the hand. On conducting a literature search, we were unable to find any studies that investigated the association between subungual hematomas, fractures, and the presence of an occult laceration of the nail bed requiring repair. Forty-seven consecutive patients who presented to the emergency department with subungual hematoma involving more than one fourth of the nail bed were included in this study. In these cases, radiographs were taken, and the nail was lifted to look for a laceration. In the subgroup of patients who had subungual hematoma associated with a fracture, all of them had a laceration requiring repair. Patients with a subungual hematoma greater than one half of the size of the nail bed had a 60% incidence of a laceration requiring repair. The authors believe that patients presenting with a subungual hematoma involving greater than one half of the nail surface and a fracture of the distal phalanx should have the nail lifted and the nail bed explored and repaired.

Use of intravenous pyelography in blunt trauma--a reappraisal.

The role of intravenous pyelography (IVP) in the evaluation of blunt abdominal trauma is controversial. Major renal injuries have occasionally been reported in the absence of hematuria, but the test is not always accurate, is expensive and has potential morbidity. By reviewing the charts of 150 consecutive patients seen in an emergency department who had IVP for blunt abdominal trauma, we evaluated the ability of clinical and laboratory findings to predict IVP findings, the incidence of abnormal findings on IVP and the number of times IVP affected patient management. Only one patient's management was found to be clearly affected by the results of the IVP. We feel, therefore, that IVP should be reserved in cases of blunt abdominal trauma for patients with gross hematuria and those with microscopic hematuria and suggestive clinical findings. The absence of hematuria should preclude the use of IVP unless there are other exceedingly strong clinical findings.