Brain tumor-targeted drug delivery strategies

Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood-brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

Ultrastructural observation on pulmonary fibrosis in E9 rats treated with compound Carapax trionycis formula

OBJECTIVE@#To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compound Carapax trionycis (C. trionycis; Biejia in Chinese) formula.@*METHODS@#Sixty male Sprague-Dawley rats were randomly divided into four groups (n=15): compound C. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin. Five rats from each group were sacrificed on day 7, 14 and 28 of the drug treatment, respectively. The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy. The Szapiel's method was used to assess the degree of alveolitis and pulmonary fibrosis.@*RESULTS@#Compared with the model group, the compound C. trionycis formula groups had slighter pulmonary alveolitis after the 7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the 14-day treatment. After the 28-day treatment, the compound C. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than 21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than 51% of the whole lung area.@*CONCLUSIONS@#The compound C. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.

Phentolamine antagonizes the effects of norepinephrine on the activity of pain-related neurons in the parafascicular nucleus of morphine-dependent rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine the antagonization of phentolamine against the effects of norepinephrine (NE) on the activity of pain-related neurons in the parafascicular nucleus of morphine-dependent rats.</p><p><b>METHODS</b>Electric impulses were applied as nociceptive stimulus to the right sciatic nerve of morphine-dependent rats, and the discharges of the pain-related neurons in the parafascicular nucleus were recorded by extracellular recording method with glass microelectrodes.</p><p><b>RESULTS</b>Intracerebroventricular injection of norepinephrine resulted in the inhibition of evoked response of the pain-excited neurons as well as the excitation of evoked response of the pain-inhibiting neurons. Both the inhibitory effect on the electric discharges of the pain-excited neurons and the excitatory effect on the pain-inhibiting neurons of norepinephrine were almost completely blocked by intracerebroventricular administration of phentolamine.</p><p><b>CONCLUSION</b>Phentolamine antagonizes the inhibitory effect of norepinephrine on the activity of pain-related neurons in the parafascicular nucleus in morphine-dependent rats, and norepinephrine may play an important role in the integration of the pain signal through the alpha-receptors.</p>

Modulation of gamma-aminobutyric acid on painful sense in central nervous system of morphine-dependent rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To observe the effects of gamma-aminobutyric acid (GABA) on the electric activities of pain-excited neurons (PEN) in nucleus accumbens (NAc) in central nervous system (CNS) of morphine-dependent rats.</p><p><b>METHODS</b>After GABA or the GABA(A)-receptor antagonist, bicuculline (Bic), was injected into cerebral ventricles or NAc, right sciatic nerve was stimulated by electrical pulses, which was considered as traumatic pain stimulation. Extracellular recordings methods were used to record the electric activities of PEN in NAc.</p><p><b>RESULTS</b>When GABA was injected into intracerebroventricle (ICV) as well as NAc, it could decrease the pain-evoked discharge frequency and prolong the latency of PEN. Bic could interdict the above effects of GABA on the electric activities of PEN.</p><p><b>CONCLUSION</b>Exogenous GABA might have an inhibitory effect on the central pain adjustment. Furthermore, GABA and GABA(A) receptor participate and mediate the traumatic information transmission process in CNS.</p>

Differential effects of dopamine on pain-related electric activities in normal rats and morphinistic rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the influence of dopamine (DA) and DA receptor's antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats.</p><p><b>METHODS</b>The influence of DA on the electric activity of the pain-excited neuron (PEN) in the caudate nucleus (Cd) of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated.</p><p><b>RESULTS</b>DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats.</p><p><b>CONCLUSION</b>The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.</p>

Effect of acetylcholine on pain-related electric activities in hippocampal CA1 area of normal and morphinistic rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To examine the effect of acetylcholine (ACh) on the electric activities of pain-excitation neurons (PEN) and pain-inhibitation neurons (PIN) in the hippocampal CA1 area of normal rats or morphinistic rats, and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.</p><p><b>METHODS</b>The trains of electric impulses applied to sciatic nerve were set as noxious stimulation. The discharges of PEN and PIN in the CA1 area were recorded extracellularly by glass microelectrode. We observed the influence of intracerebroventricular (i.c.v.) injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.</p><p><b>RESULTS</b>Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats. In normal rats, ACh decrease the pain-evoked discharge frequency of PEN, while increased the frequency of PIN. These effects reached the peak value at 4 min after injection of ACh. In morphinistic rats, ACh also inhibited the PEN electric activity and potentialized the PIN electric activity, but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.</p><p><b>CONCLUSION</b>Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation. Morphine addiction attenuated the sensitivity of pain-related neurons to the noxious information.</p>

Clinical features of idiopathic ventricular tachycardia of various types and their radiofrequency ablation therapy / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the clinical features idiopathic ventricular tachycardia (IVT) and evaluate the effect of radiofrequency ablation therapy for their management.</p><p><b>METHODS</b>An retrospective analysis was conducted in 165 IVT patients who received radiofrequency ablation therapy. IVT was classified into 3 types according to the site of origin, namely the right ventricular outflow tract (RVOT-IVT, 86 cases), left ventricular septum (LV-IVT, 75 cases), and left Valsalva sinus (4 cases).</p><p><b>RESULTS AND CONCLUSION</b>RVOT-IVT was more frequent in female patients than in male patients (60 vs 26, M/F ratio of 0.43). In LV-IVT, male patients prevailed (54 vs 21, M/F ratio of 2.57), suggesting a gender difference in the incidence of IVT. IVT occurred mainly in young and middle-age patients. Most RVOT-IVT occurred in the third to fourth decade of life (mean 36-/+12 years), and LV-IVT occurred at a younger age than did RVOT-IVT (mean 26-/+15 years, P<0.01). Twelve-lead ECGs revealed left bundle branch block morphology in RVOT-IVT, and most of them presented with frequent premature ventricular contraction and/or non-sustained ventricular tachycardia. All the RVOT-IVT patients were successfully ablated by radiofrequency energy in pace mapping. LV-IVT patients with right bundle branch block morphology presented sustained ventricular tachycardia for most of the time, and 97% of the patients were successfully managed with radiofrequency ablation in activation mapping. Four IVT patients were characterized by atypical bundle branch block, an inferior axis, and an R/S ratio >1 in lead V3 or V2, and their tachycardia was ablated successfully in the left sinus of Valsalva using pace mapping. Radiofrequency ablation is currently an effective procedure for IVT management.</p>

Influence of glutamate and NMDA-receptor antagonist MK-801 on the electric activities of pain-excitation neurons in the nucleus accumbens of rats / 生理学报

The experiment explored the influence of glutamic acid (Glu) and the NMDA-receptor antagonist dizocilpine maleate (MK-801) on the pain-evoked responses of pain-excitation neurons (PEN) in the nucleus accumbens (NAc) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN in NAc were recorded by glass microelectrode. We observed the influence of intracerebroventricular (icv) injection of Glu and microinjection of MK-801 into the NAc on the noxious stimulation-evoked activities of PEN in NAc. The results showed that the noxious stimulation potentiated the electric activities of PEN in NAc. Intracerebroventricular injection of Glu (10 nmol/10 microl) increased the frequency of the discharge of PEN evoked by the noxious stimulation in NAc, the Glu-induced response was blocked by the injection of MK-801 (1.0 nmol/0.5 microl) into NAc. MK-801 partly inhibited the response of PEN upon the noxious stimulation. It is therefore suggested that the facilitatory effect of Glu on PEN response in NAc to the noxious stimulation is mediated by NMDA receptors, and that Glu and NMDA receptors are involved in the modulation of nociceptive information transmission in the NAc.

The relation between amygdaloid nucleus in rats and pain modulation / 中国应用生理学杂志

<p><b>AIM</b>To research the influence of noxious stimuli on the electric activities of pain-related neurons in several subnuclei of Amygdaloid Nucleus in rats.</p><p><b>METHODS</b>Trains of the electric impulses applied to the sciatic nerve were used as noxious stimuli. The discharges of neurons were channeled off by glass microelectrode.</p><p><b>RESULTS</b>Pain-related neurons existed in several subnuclei of Amygdaloid Nucleus. When the noxious stimuli were administered the frequency of discharges of pain-excited neurons (PEN) was increased while the frequency of pain-inhibited neurons (PIN) was decreased to the lowest level. The electric activities of PEN and PIN were matched with each other. Intraperitoneal injection of morphine (10 mg/kg) antagonized the effects of noxious stimuli on the pain-related neurons.</p><p><b>CONCLUSION</b>Several subnuclei of Amygdaloid Nucleus play an essential role in perceiving, integrating and transmitting the pain impulses. They are a part of the central nervous system in which pain information is controlled and managed.</p>

Establishment and evaluation of hematology review criteria for action following automated complete blood counts and leukocytes differential / 中华检验医学杂志

Objective To establish and evaluate criteria applied to review of complete blood counts (CBC)and differential results from automated hematology analyzers.Methods Temporary criteria were established by using alarm system of XE-2100 automated hematology analyzer and by consulting the 41 suggested rides of international consensus group.2 795 out-and in-patient samples were run as clinical samples.Stained blood films were prepared and manual differential with smear review were performed on all samples.Statistical analysis was done for each temporary rule and instrument flag which indicated abnormal cell quantity and morphology.Results Of all rules,instrument flags of ‘Immature Gran/Left Shift?’, ‘ Atypical Lympho?’and‘NRBC(nucleated red blood cell)?’showed most frequent false positive and false negative instrument flag.Evaluation on rnles about cell quantity change showed false positive and false negative rates were both low.Results of morphology evaluation showed that true positive rate was 17.44%, false positive rate was 15.82%,true negative rate was 63.49%,false negative rate was 3.25%.‘ Atypical Lymphocyte?’,‘Immature Gran?’and‘blast?’were the most frequent false positive flags.According to those results and clinicians opinions,our hematology review criteria for action following automated CBC and leukocytes differential was established.Conclusions The hematology review criteria have high true positive rate and low false negative rate.To clinical hematology laboratory using automated hematology analyzer,new criteria can reduce work load,bring lower false negative rate and higher work efficiency.

Analysis of polymorphism in human cDNA sequence of prothymosin-? / 第二军医大学学报

Objective:To analyze the polymorphism in human cDNA sequence of prothymosin-?(ProT?)by sequencing analysis.Methods:The cDNA of human ProT? was amplified from cells of peripheral blood and cord blood by RT-PCR.The product of RT-PCR was purified and linked with vector pMD18-T.After cloning and sequencing,the sequence of ProT? cDNA was compared with the standard sequence to analyze the polymorphism in the ProT? cDNA sequence.Results:The cloned ProT? cDNA sequence was different from that of the standard.We found 2 kinds of variations:(1)The nucleotide in 107 position was varied and the nucleotides in 110-121 and 191-205 positions were deleted;(2)The nucleotide in 306 position was deleted,mainly in the 60-80 years old group.Conclusion:We have identified 2 kinds of variations in human ProT? cDNA,but the first 28 amino acid in the N-terminal of cDNA of human ProT? are not involved therefore the variations do not affect the function of human ProT?.