Short communication: Characterization of molasses chemical composition.

Beet and cane molasses are produced worldwide as a by-product of sugar extraction and are widely used in animal nutrition. Due to their composition, they are fed to ruminants as an energy source. However, molasses has not been properly characterized in the literature; its description has been limited to the type (sugarcane or beet) or to the amount of dry matter (DM), total or water-soluble sugars, crude protein, and ash. Our objective was to better characterize the composition of cane and beet molasses, examine possible differences, and obtain a proper definition of such feeds. For this purpose, 16 cane and 16 beet molasses samples were sourced worldwide and analyzed for chemical composition. The chemical analysis used in this trial characterized 97.4 and 98.3% of the compounds in the DM of cane and beet molasses, respectively. Cane molasses contained less DM compared with beet molasses (76.8 ± 1.02 vs. 78.3 ± 1.61%) as well as crude protein content (6.7 ± 1.8 vs. 13.5 ± 1.4% of DM), with a minimum value of 2.2% of DM in cane molasses and a maximum of 15.6% of DM in beet molasses. The amount of sucrose differed between beet and cane molasses (60.9 ± 4.4 vs. 48.8 ± 6.4% of DM), but variability was high even within cane molasses (39.2-67.3% of DM) and beet molasses. Glucose and fructose were detected in cane molasses (5.3 ± 2.7 and 8.1 ± 2.8% of DM, respectively), showing high variability. Organic acid composition differed as well. Lactic acid was more concentrated in cane molasses than in beet molasses (6.1 ± 2.8 vs. 4.5 ± 1.8% of DM), varying from 1.6 to 12.8% of DM in cane molasses. Dietary cation-anion difference showed numerical differences among cane and beet molasses (7 ± 53 vs. 66 ± 45 mEq/100 g of DM, on average). It varied from -76 to +155 mEq/100 g of DM in the cane group and from +0 to +162 mEq/100 g of DM in the beet group. Data obtained in this study detailed differences in composition between sources of molasses and suggested that a more complete characterization could improve the use of molasses in ration formulation.

Lactose oleate as new biocompatible surfactant for pharmaceutical applications.

Sugar fatty acid esters are an interesting class of non-ionic, biocompatible and biodegradable sugar-based surfactants, recently emerged as a valid alternative to the traditional commonly employed (e.g. polysorbates and polyethylene glycol derivatives). By varying the polar head (carbohydrate moiety) and the hydrophobic tail (fatty acid), surfactants with different physico-chemical characteristics can be easily prepared. While many research papers have focused on sucrose derivatives, relatively few studies have been carried out on lactose-based surfactants. In this work, we present the synthesis and the physico-chemical characterization of lactose oleate. The new derivative was obtained by enzymatic mono-esterification of lactose with oleic acid. Thermal, surface, and aggregation properties of the surfactant were studied in detail and the cytotoxicity profile was investigated by MTS and LDH assays on intestinal Caco-2 monolayers. Transepithelial electrical resistance (TEER) measurements on Caco-2 cells showed a transient and reversible effect on the tight junctions opening, which correlates with the increased permeability of 4 kDa fluorescein-labelled dextran (as model for macromolecular drugs) in a concentration dependent manner. Moreover, lactose oleate displayed a satisfactory antimicrobial activity over a range of Gram-positive and Gram-negative bacteria. Overall, the obtained results are promising for a further development of lactose oleate as an intestinal absorption enhancer and/or an alternative biodegradable preservative for pharmaceutical and food applications.

Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

BACKGROUND: Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. METHODS: In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. RESULTS: Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. CONCLUSION: This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

Time course of CT evolution in traumatic subarachnoid haemorrhage: a study of 141 patients.

BACKGROUND: Evidence of tSAH on an admission CT scan seems to be an early predictor of evolving posttraumatic lesions. Detection of these changes requires serial CT scanners. The goal of our study was to determine the optimal timing of follow-up CT scans in head injured patients with traumatic subarachnoid haemorrhage (tSAH). METHOD: We reviewed the initial and follow-up CT scans in 141 patients with closed head injuries and evidence of tSAH on the initial CT scan. We used the Marshall classification to determine diffuse and focal injuries. The "worst CT scan", defined as the CT examination in which midline shift, cistern compression and/or intracranial focal lesions were greater, was also determined. Any worsening of the admission CT findings, occurring when the "worst CT examination" did not correspond to the initial CT study, was considered as a "CT evolution". Any "CT evolution" associated with a variation from a lower to a higher score in the Marshall classification score was indicated as a "significant CT evolution". FINDINGS: The median time between injury and the first CT scan was 1.3 (IQR 1.5) hours. A CT evolution was found in 83/141 (58.9%) patients in whom the median time between the initial and worst CT scans was 27.7 hours (IQR 69.2 hours). The worst CT studies were seen more often at 12-24 hours and at 24-48 hours after the admission CT scan than in later studies. A similar temporal profile was observed when the timing of the "worst CT scan" was evaluated in 38/83 (45.8%) subjects with a "significant CT evolution". INTERPRETATION: Our findings show that an early admission CT scan did not represent the full extent of the posttraumatic damage in more than half of our patients. They also suggest that to identify these changes in head injured patients with tSAH, CT scans should be repeated at 12-24 and possibly also at 24-48 hours from the admission CT examination to allow early detection and evacuation of evolving intracranial lesions.

Stapes surgery and psychiatric complications.

Changes in auditory perception can cause disturbances in development and personality. This phenomenon has been studied in particular in children hearing loss or in progressive or sudden hearing loss in the adult. We present the case of a patient with psychobehavioural alterations after restoration of hearing following a small fenestra stapedectomy for bilateral otosclerosis with moderate-severe hearing impairment. The diagnosis, physiopathology and medicolegal implications are discussed.

Acute phase responses and cytokine secretion in chronic fatigue syndrome.

This study addresses the hypothesis that clinical manifestations of chronic fatigue syndrome (CFS) are due in part to abnormal production of or sensitivity to cytokines such as interleukin-1beta (IL-1beta) and IL-6 under basal conditions or in response to a particular physical stress: 15 min of exercise consisting of stepping up and down on a platform adjusted to the height of the patella. The study involved 10 CFS patients and 11 age-, sex-, and activity-matched controls: of these, 6 patients and 4 controls were tested in both the follicular and the luteal phases of the menstrual cycle, and the remainder were tested in only one phase, for a total of 31 experimental sessions. Prior to exercise, plasma concentrations of the acute phase reactant alpha2-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls. Secretion of IL-6 was generally higher for CFS patients (approximately 38%), however, this difference was statistically significant only if all values over a 3-day period were analyzed by repeated-measures ANOVA (P = 0.035). IL-6 secretion correlated with plasma alpha2-macroglobulin in control subjects at rest (R = 0.767, P = 0.001). Immediately after exercise, the CFS patients reported greater ratings of perceived exertion (P=0.027) compared to the healthy control subjects. Ratings of perceived exertion correlated with IL-1beta secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients, and IL-1beta secretion was not different between groups. Exercise induced a slight (< 12%) but significant (P = 0.006) increase in IL-6 secretion, but the responses of the CFS patients were not different than controls. Furthermore, no significant exercise-induced changes in body temperature or plasma alpha2-macroglobulin were observed. These data indicate that under basal conditions, CFS is associated with increased IL-6 secretion which is manifested by chronically elevated plasma alpha2-macroglobulin concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant factor in the pathogenesis of CFS.

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome.

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion. For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively). These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome.

Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which include fatigue, myalgia, and low-grade fever, are similar to those experienced by patients infused with cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular secretion of interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-1 receptor type II (IL-1sRII) is abnormal in female CFS patients compared to age- and activity-matched controls; (2) that these abnormalities may be evident only at certain times in the menstrual cycle; and (3) that physical exertion (stepping up and down on a platform for 15 min) may accentuate differences between these groups. Isolated peripheral blood mononuclear cells from healthy women, but not CFS patients, exhibited significant menstrual cycle-related differences in IL-1 beta secretion that were related to estradiol and progesterone levels (R2 = 0.65, P < 0.01). IL-1Ra secretion for CFS patients was twofold higher than controls during the follicular phase (P = 0.023), but luteal-phase levels were similar between groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients compared to controls (P = 0.002). The only changes that might be attributable to exertion occurred in the control subjects during the follicular phase, who exhibited an increase in IL-1 beta secretion 48 hr after the stress (P = 0.020). These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradiol and progesterone. Furthermore, the increased release of IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated with chronic, low-level activation of the immune system.

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome.

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue syndrome. Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from 49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2, P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age. In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis.

Immunoglobulin subclass levels in chronic fatigue syndrome.

The levels of immunoglobulin subclasses were determined for 46 patients meeting the original Centers for Disease Control case definition of chronic fatigue syndrome and were compared to values obtained for 50 age- and gender-matched healthy volunteer blood donor controls. The levels of immunoglobulin subclasses in these groups were further compared to a third group of additional chronic fatigue syndrome cases from whom samples had been obtained and frozen prospectively over a period of 7 years. These data do not demonstrate significant immunoglobulin subclass deficiencies in patients with chronic fatigue syndrome.

Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups.

PURPOSE: To measure the functional status and well-being of patients with chronic fatigue syndrome (CFS), and compare them with those of a general population group and six disease comparison groups. PATIENTS AND METHODS: The subjects of the study were patients with CFS (n = 223) from a CFS clinic, a population-based control sample (n = 2,474), and disease comparison groups with hypertension (n = 2,089), congestive heart failure (n = 216), type II diabetes mellitus (n = 163), acute myocardial infarction (n = 107), multiple sclerosis (n = 25), and depression (n = 502). We measured functional status and well-being using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which is a self-administered questionnaire in which lower scores are indicative of greater impairment. RESULTS: Patients with CFS had far lower mean scores than the general population control subjects on all eight SF-36 scales. They also scored significantly lower than patients in all the disease comparison groups other than depression on virtually all the scales. When compared with patients with depression, they scored significantly lower on all the scales except for scales measuring mental health and role disability due to emotional problems, on which they scored significantly higher. The two SF-36 scales reflecting mental health were not correlated with any of the symptoms of CFS except for irritability and depression. CONCLUSION: Patients with CFS had marked impairment, in comparison with the general population and disease comparison groups. Moreover, the degree and pattern of impairment was different from that seen in patients with depression.

Cognitive deficits in patients with chronic fatigue syndrome.

Twenty-nine subjects with chronic fatigue syndrome (CFS) and 25 healthy control subjects were administered a lengthy neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. The primary significant differences between patients and controls were found on tests of learning and memory. These differences remained when the degree of psychiatric symptomatology in the subjects was covaried. Patients on and off psychoactive medications did not differ in their performance on these tasks. These results suggest that at least a subset of CFS patients may experience significant impairments in learning and memory.

An examination of the working case definition of chronic fatigue syndrome.

PURPOSE: Chronic fatigue syndrome (CFS) currently is defined by a working case definition developed under the leadership of the United States Centers for Disease Control and Prevention (CDC) based on a consensus among experienced clinicians. We analyzed the experience from one large center to examine the adequacy of the case definition. PATIENTS AND METHODS: Predefined clinical and laboratory data were collected prospectively from 369 patients with debilitating fatigue, of whom 281 (76%) met the major criteria of the original CDC case definition for CFS: (1) fatigue of at least 6 months' duration, seriously interfering with the patient's life; and (2) without evidence of various organic or psychiatric illnesses that can produce chronic fatigue. The same clinical data were obtained from 311 healthy control subjects and two comparison groups with diseases that can present in a similar fashion; relapsing-remitting multiple sclerosis (n = 25) and major depression (n = 19). RESULTS: All of the minor criteria symptoms from the original CDC case definition distinguished patients with debilitating chronic fatigue from healthy control subjects, and many distinguished the patients with chronic fatigue from the comparison groups with multiple sclerosis and depression: myalgias, postexertional malaise, headaches, and a group of infectious-type symptoms (ie, chronic fever and chills, sore throat, swollen glands in the neck or underarm areas). In addition, two other symptoms not currently part of the case definition discriminated the chronic fatigue patients from the control/comparison groups: anorexia and nausea. Physical examination criteria only infrequently contributed to the diagnosis. Patients meeting the CDC major criteria for CFS also met the minor criteria in 91% of cases. CONCLUSION: Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

Absence of parvovirus B19 infection in chronic fatigue syndrome.

OBJECTIVE: To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities. METHODS: Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus. RESULTS: No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened. CONCLUSION: Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.

Vestibular function test anomalies in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described. Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis rotation (EVA) gains at the higher frequencies tested. As a group, the average gain of EVA was significantly lower than normals in the 0.1 - 1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s. Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.

Diffuse axonal injury with brainstem localisation: report of a case in a mild head injured patient.

The authors present the case of a 26-yrs-old woman admitted into our hospital after a severe polytrauma with a mild head injury. CT scanning disclosed two small hemorrhages located in her brainstem and mesial temporal lobe. After splenectomy the patient made a full recovery without neurological sequelae. Radiological signs of diffuse axonal injury even in the brainstem may be present in a clinically mild head injury.

Arachnoid cyst of middle cranial fossa and ipsilateral subdural haematoma: diagnostic and therapeutic implications in three cases.

We describe three cases of arachnoid cyst of the middle cranial fossa with associated intracystic and subdural haematomas. In all of the patients the diagnosis was made before surgical treatment. No bleeding could be attributed to ruptured bridging veins. In two cases the source of bleeding was identified at the interface between the dura mater and the outer membrane at the temporal skull base. We suggest that, even if wide outer membrane membranectomy is probably not indicated, careful coagulation of the membrane at the skull base is necessary to avoid bleeding within the cyst.