Concentrations, influencing factors, risk assessment methods, health hazards and analyses of polycyclic aromatic hydrocarbons in dairies: a review.

The occurrence of polycyclic aromatic hydrocarbons (PAHs) in dairies has been widely reported. Consumers may be overly exposed to PAHs through dairies causing health risks. Hazards can be reduced by controlling influencing factors in the full-chain of dairy production. This review briefly introduces research trends and analytical methods concerning PAHs in dairies. Additionally, this review discusses influencing factors of PAH concentrations in various dairies to avoid PAHs' formation and accumulation during manufacture. Relevant regulations are referred to and the reported risk assessment methods are summarized. Furthermore, indicators of health risks including TEQBaP, the number and the rate of over-standard are calculated based on PAH concentrations. Through analyses, we find PAH and BaP contamination in dairies are complex problems depending on environment, processing and storage. There was a significant correlation between fat contents and PAH concentrations. Results of infant formula in certain research were worrying and those of smoked cheeses are remarkably high indicating the dangerous smoking process. It is significant to monitor PAHs and calculate TEQBaP from meadows to feeders. Moreover, the existing regulations are insufficient and need strengthening. The data and discussions in this review contribute to worldwide Big Data, further scientific investigation and regulations for PAHs in dairies.

Reversible Splenial Lesion Syndrome (RESLES) After Chemotherapy of Oral Tegafur-uracil in a Female With Locally Rectal Adenocarcinoma.

A 42-year-old woman with reversible splenial lesion syndrome (RESLES) and rectal adenocarcinoma presented with sudden-onset delirium after the sixth cycle of her chemotherapy drug, oral tegafur-uracil (300 mg/m/day, days 1-14, with treatment cycle repeated every 21 days). Accompanied by the anti-CV2 antibody, paraphasia, and a loss of bimanual coordination, the patient's etiology and clinical manifestations of RESLES are unlike those of other reported cases of RESLES. Tegafur-uracil is an oral fluoropyrimidine that has a similar effect to 5-fluorouracil as an adjuvant treatment for colorectal cancer. The possibility that the toxicity of chemotherapeutic drugs may play a role in the pathogenesis of cytotoxic edema in the splenium of the corpus callosum and extracallosal white matter should be investigated further.

Simultaneous Determination of Typical Chlorinated, Oxygenated, and European Union Priority Polycyclic Aromatic Hydrocarbons in Milk Samples and Milk Powders.

An increasing number of studies have suggested that PAH contamination in dairy products demands high concern. This study established an efficient determination method for the European Union 15 + 1 PAHs and four PAH derivatives in dairy samples using a QuEChERS method coupled with GC-QqQ-MS. The optimized method obtained a recovery of 63.38-109.17% with a precision of 3.82-15.62%, and the limit of detection and limit of quantification were 0.08-0.78 and 0.27-2.59 µg/kg, respectively. The validated method was then successfully applied to identify the 20 PAHs in 82 dairy samples, including 43 commercial milk samples and 39 milk powders. The total PAH concentrations ranged from 2.37 to 11.83 µg/kg, and benzo[a]pyrene was only quantified in one milk and one milk powder sample at 0.35 and 0.42 µg/kg, respectively. The concentrations of PAH4 in milk samples and milk powders were not quantified (nq)-3.99 and nq-4.51 µg/kg, respectively. The results confirmed the appreciable occurrence of PAHs in dairy products, especially in infant formula. The data in this study provide a scientific basis for assessment on origin tracing, dietary exposure, and health risk of PAHs and their derivatives.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats.

BACKGROUND: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. OBJECTIVE: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. METHODS: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. RESULTS: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. CONCLUSION: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome with hypothyroidism and psychiatric disorders.

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a clinical syndrome associated with mitochondrial disorders (MIDs). This report illustrates a case of MELAS syndrome with hypothyroidism and psychiatric disorders, which is different from the common clinical manifestations of MELAS syndrome, such as exercise intolerance, migraine-like headaches, hearing loss and seizures etc. There are considerable interests in the possibility that mitochondrial dysfunction may play a role in the pathogenesis of endocrine dysfunctions and psychiatric disorders in MELAS syndrome.

Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats.

The benzodiazepine diazepam impairs memory and long-term potentiation (LTP) in the hippocampus. Here, we investigate the effect of diazepam on LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in urethane-anesthetized Sprague--Dawley rats. Diazepam was applied locally at the recording spinal segments before and after LTP induction by tetanic stimulation. We found (1) Diazepam completely blocked LTP induction. (2) Diazepam and midazolam reversed spinal LTP, when applied at 30 min after LTP induction and depressed but could not reverse spinal LTP, when applied at 3 h after LTP induction. (3) Pretreatment with benzodiazepine receptor antagonist flumazenil or GABA(A) receptor antagonist bicuculline completely blocked the inhibitory effects of diazepam on spinal LTP. In contrast, when the inhibitory effect of diazepam was fully established, neither of these antagonists was capable of reversing the inhibition by diazepam. (4) Spinal application of the GABA(A) receptor agonist 3-amino-1-propanesulfonic acid (3-APSA) at a dose of 50 microg, produced a transient inhibition of spinal LTP. These results suggest that diazepam might prevent and depress spinal plastic change produced by noxious stimulation via activation of the GABA(A) -benzodiazepine receptor complex.

Clonidine depresses LTP of C-fiber evoked field potentials in spinal dorsal horn via NO-cGMP pathway.

Clonidine, a specific alpha2-adrenergic receptor agonist, has been found to be effective for the treatment of neuropathic pain, the mechanism underlying the effect is, however, not well understood. Here, the effect of clonidine on long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn, which is a synaptic model of injury-induced hyperalgesia, was investigated. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in anesthetized adult Sprague-Dawley rats. Clonidine and other substances were applied locally at the recording spinal segments before or after LTP induction by tetanic stimulation. We found that (1) Clonidine completely blocked LTP induction, when applied 30 min before tetanic stimulation and depressed spinal LTP, when applied 30 min and 3 h after LTP induction. (2) The inhibitory effect of clonidine on spinal LTP had two phases: a fast phase lasting for about 3.5 h and a slow phase persisting for the rest time of experiments (up to 8 h after drug). (3) Spinal clonidine at low dose (10.7 micro g/100 micro l) depressed spinal LTP but not C-fiber baseline response and at higher dose (107 micro g/100 micro l) depressed both of them. (4) Pretreatment with alpha2-adrenergic receptor antagonist yohimbine completely blocked the inhibitory effect of clonidine. (5) Pretreatment with muscarinic receptor antagonist atropine, nitric oxide synthesis inhibitor l-NNA or cGMP inhibitor ODQ depressed the fast phase inhibition significantly and abolished the slow phase inhibition completely. These results suggest that clonidine may exert analgesic effect by depressing the synaptic plasticity in spinal dorsal horn, via activation of muscarinic receptor-NO-cGMP pathway.

Retraction. Clc-2 knockout attenuated experimental temporal lobe epilepsy in mice by tonic inhibition mediated by GABAA receptors.

Temporal lobe epilepsy (TLE), the most prevalent form of epilepsy, is often associated with drug-resistant seizures. In TLE, altered function of γ-aminobutyric acid (GABA)A receptors (GABAARs) results in potentiation of excitatory and/or failure of inhibitory neurotransmission, which contributes to seizure induction and propagation. Our previous study suggested that chloride channel-2 (Clc-2) contributed to chronically elevated tonic inhibition mediated by GABAARs in a rat model of TLE. In the present study, we used Clc-2 knockout mice to investigate further the role of Clc-2 and its interaction with tonic GABAergic inhibition in a model of TLE. The results revealed that knockout of Clc-2 decreased tonic seizure protection, latency of clonic seizure, seizure threshold and mortality protection in mice. Clc-2 knockout decreased the action potential (AP)peak and APthreshold, Clc-2 currents and GABAAR-mediated tonic inhibition in CA1 pyramidal neurons. Thus, the voltage-gated chloride channel Clc-2, which was functionally upregulated in CA1 pyramidal cells after seizures, may provide protection against TLE by its regulation of action potentials, Clc-2 currents and GABAARs in the CA1 region of the hippocampus.

Chronic treatment with levetiracetam reverses deficits in hippocampal LTP in vivo in experimental temporal lobe epilepsy rats.

Temporal lobe epilepsy (TLE), the common form of epilepsy in adults, often displays complex partial seizures and cognitive deficits. The underlying mechanisms of such deficits are not yet well understood. Many contributing factors, such as initial epileptogenic lesion, seizure type, age of onset, and treatment side effects have been proposed. Levetiracetam (LEV) is a novel anti-epileptic drug (AED) used to treat partial seizures and idiopathic generalized epilepsy. It has been suggested that LEV exerts antiepileptic properties by modulation of synaptic release of neurotransmitters. However, its neuroprotective effects on learning and memory are not yet well demonstrated. Here we showed the impairment of spatial memory in the pilocarpine-induced experimental TLE rats, which can be improved by LEV. Furthermore, we found chronic LEV treatment partially reversed the SE-induced synaptic dysfunction in hippocampal LTP induction in vivo. In addition, LEV treatment can alleviate the SE-induced abnormal GluR1 phosphorylation at Ser(831) site, which may contribute to the rescue of synaptic transmission. These results indicate the neuroprotective role for LEV while it exhibits an antiseizure effect on experimental epileptic models.

The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy.

Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P < 0.05). Levetiracetam reduced serum activities of PON1 and ARE (P < 0.05) and led to markedly increased serum levels of ox-LDL (P < 0.05). Serum concentrations of hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P < 0.05). Levetiracetam treatment had a clear beneficial effect on the overall quality of life (QOL) scores of the patients, as indicated by significantly improved cognitive functioning, behavior problems, emotional conditioning, physical condition, social functioning, self-assessed life quality score, self-assessed health score, and the total QOL score (P < 0.05). Levetiracetam can improve life quality of patients with refractory epilepsy, decrease NPY and GAL in plasma and cerebrospinal fluid, serum PON1 and ARE activities, and serum levels of ox-LDL, hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy.

24-h residual urine volume at hemodialysis initiation: a possible predictor for acute ischemic stroke incurrence in hemodialysis patients.

BACKGROUND: Residual renal function (RRF) recently has been confirmed to be a significant predictor of morbidity and mortality in hemodialysis (HD) patients. As RRF is not exactly the same with 24-h residual urine volume, the aim of our study is to evaluate the association of residual urine volume with acute ischemic stroke (AIS) among HD patients. METHODS: 282 patients starting chronic HD in our center during January 2005 and December 2008 were enrolled. The clinical data at HD initiation and the occurrence of AIS since starting HD were recorded and obtained from our database. According to the prevalence of AIS, we divided 282 patients into the AIS group (n=69) and non-AIS (n=213) group. RESULTS: A total of 69 (24.5%) patients suffered from AIS since HD initiation. Patients with AIS were much older, with more diabetes, had higher levels of hemoglobin, while lower levels of residual urine volume and serum uric acid. In multivariate logistic regression analysis, old age (OR, 1.036; 95% CI, 1.009-1.063; P=0.008), diabetes (OR, 2.385; 95% CI, 1.074-5.294; P=0.033) and 24-h residual urine volume<1290 ml at HD initiation (OR, 2.446; 95% CI, 1.219-4.907; P=0.012) was significant predictors for future AIS occurrence during HD. CONCLUSION: This study indicates that residual urine volume levels at HD initiation are inversely associated with AIS risk in future in chronic HD patients. Besides, aging and diabetes should also be noticed for prevention of AIS.

p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury.

Compelling evidence shows that the adjacent uninjured primary afferents play an important role in the development of neuropathic pain after nerve injury. The underlying mechanisms, however, are largely unknown. In the present study, the selective motor fiber injury was performed by L5 ventral root transection (L5 VRT), and p38 activation in dorsal root ganglia (DRG) and L5 spinal dorsal horn was examined. The results showed that phospho-p38 immunoreactivity (p-p38-IR) was increased in both L4 and L5 DRGs, starting on day 1 and persisting for nearly 3 weeks (P<0.05) following L5 VRT and that the activated p38 was confined in neurons, especially in IB4 positive C-type neurons. L5 VRT also induced p38 activation in L5 spinal dorsal horn, occurred at the first day after the lesion and lasted for 2 weeks (P<0.05). The activated p38 is restricted entirely in spinal microglia. In contrast, selective injury of sensory neurons by L5 dorsal root transection (L5 DRT) failed to induce behavioral signs of neuropathic pain and activated p38 only in L5 DRG but not in L4 DRG and L5 spinal dorsal horn. Intraperitoneal injection of thalidomide, an inhibitor of TNF-alpha synthesis, prevented p38 activation in DRG and spinal cord. Intrathecal injection of p38 inhibitor SB203580, starting before L5 VRT, inhibited the abnormal pain behaviors. Post-treatment with SB203580 performed at the 1st day or at the 8th day after surgery also reduced established neuropathic pain. These data suggest that p38 activation in uninjured DRGs neurons and in spinal microglia is necessary for the initiation and maintenance of neuropathic pain induced by L5 VRT.