Clinical and radiological outcomes of concomitant endoscopic gastrocnemius release with scarf osteotomy

Background

Studies showed patients with hallux valgus also have tight gastrocnemius concomitantly. This study aims to investigate (1) prevalence of tight gastrocnemius in symptomatic hallux valgus (2) clinical and radiological outcomes of concomitant endoscopic gastrocnemius release with scarf osteotomy.

Dissemination of genetically related IMP-6-producing multidrug-resistant Pseudomonas aeruginosa ST235 in South Korea

The present study aimed to describe the prevalence and molecular epidemiology of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates obtained from non-tertiary care hospitals and geriatric hospitals in South Korea. Of the 644 isolates, 224 were carbapenem-resistant, amongst which 41 (18.3%) were MBL-producers and the major MBL type was IMP-6 (35 isolates). IMP-6-producing isolates were multidrug-resistant and showed higher minimum inhibitory concentrations for meropenem than imipenem. All of the IMP-6-producing isolates had class 1 integrons with amplification sizes of 4.5 kb/5.5 kb (34 isolates) or 3.0 kb (1 isolate); 4.5 kb/5.5 kb integrons had bla(IMP-6)-qac-aacA4-bla(OXA-1)-aadA1 (5.5 kb) and aadB-cmlA-bla(OXA-10)-aadA1 (4.5 kb). Pulsed-field gel electrophoresis (PFGE) analysis indicated that all IMP-6-producing P. aeruginosa from various geographic areas had nearly identical patterns with >85% similarity. All IMP-6-producing isolates showed high genetic similarity to those obtained from tertiary care hospitals and had the same integron type, indicating the spread of these strains to the three types of hospitals nationwide. These data show the wide spreading of clonally related IMP-6-producing P. aeruginosa (sequence type 235) through tertiary, non-tertiary and geriatric hospitals in South Korea. Continuous monitoring and thorough infection control should be performed in all types of hospitals to prevent further spreading of MBL-producing P. aeruginosa.     

Bioreducible polymer-conjugated oncolytic adenovirus for hepatoma-specific therapy via systemic administration

Systemic administration of adenovirus (Ad) vectors is complicated by host immune responses and viral accumulation in the liver, resulting in a short circulatory virus half-life, low efficacy, and host side effects. Ad surface modification is thus required to enhance safety and therapeutic efficacy. An arginine-grafted bioreducible polymer (ABP) was chemically conjugated to the Ad surface, generating Ad-ΔE1/GFP-ABP. A hepatocellular carcinoma [HCC]-selective oncolytic Ad complex, YKL-1001-ABP, was also generated. Transduction efficiency of Ad-ΔE1/GFP-ABP was enhanced compared to naked Ad-ΔE1/GFP. YKL-1001-ABP elicited an enhanced and specific killing effect in liver cancer cells (Huh7 and HepG2) expressing α-fetoprotein (AFP). Compared with naked Ad, systemic administration of ABP-conjugated Ad resulted in reduced liver toxicity and interleukin (IL)-6 production in?vitro and in?vivo. Ad-ΔE1/GFP-ABP was more resistant to the neutralizing effects of human serum compared to naked Ad-ΔE1/GFP. ABP conjugation extended blood circulation time 45-fold and reduced anti-Ad Ab neutralization. Moreover, systemic administration of YKL-1001-ABP markedly suppressed growth of Huh7 hepatocellular carcinoma. These results demonstrate that chemical conjugation of ABP to the Ad surface improves safety and efficacy, indicating that ABP-conjugated Ad is a potentially useful cancer therapeutic agent to target cancer via systemic administration.     

Cell penetrating peptide conjugated bioreducible polymer for siRNA delivery

The primary cardiomyocyte-specific peptide (PCM) and the cell-penetrating peptide (CPP), HIV-Tat (49-57), were incorporated into the polymer, cystamine bisacrylamide-diaminohexane (CBA-DAH), to increase the delivery of RNAi to target cells, specifically cardiomyocytes. Interestingly, the impact of PCM and Tat conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. We examined the potential for siRNA targeting SHP-1 or Fas to inhibit the apoptosis of cardiomyocytes under hypoxic conditions using PCM and Tat-modified poly(CBA-DAH), (PCM-CD-Tat). To evaluate for efficacy in inhibiting apoptosis, either Fas siRNA/polymer or SHP-1 siRNA/polymer were transfected into cardiomyocytes treated under hypoxic and serum-deprived conditions. After incubation under hypoxic conditions, treatment with either the SHP-1 siRNA complex or the Fas siRNA complex resulted in an increase in cell viability and a reduction in LDH-cytotoxicity. The cells transfected with either of the siRNA polyplexes had a lower incidence of apoptosis as demonstrated by Annexin V-FITC/PI staining. Both the SHP-1 siRNA/PCM-CD-Tat complex and the Fas siRNA/PCM-CD-Tat complex warrant further investigation as therapeutic agents to inhibit the apoptosis of cardiomyocytes.     

T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status

The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.     

5-Lipoxygenase Inhibition of the Fructus of Foeniculum vulgare and Its Constituents

The fruits of Foeniculum vulgare (Foeniculi Fructus) have been widely used in Chinese medicine as an antiemetic, ameliorating stomach ailments and as an analgesic. In order to establish its potential for antiallergic use, inhibitory actions of the fruiton 5-lipoxgenase (5-LOX) and β-hexosaminidase release were evaluated. The 70% ethanol extract of this plant material (FR) considerably inhibited 5-LOX-catalyzed leukotriene production from {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253"}}A23187-induced rat basophilic leukemia (RBL)-1 cells. The IC₅₀ was 3.2 μg/ml. From this extract, 12 major compounds including sabinene, fenchone, γ-terpinene, α-pinene, limonene, p-anisylacetone, p-anisylaldehyde, estragole (4-allylanisole), trans-anethole, scopoletin, bergapten and umbelliferone were isolated. And it was found that several terpene derivatives including γ-terpinene and fenchone as well as phenylpropanoid, trans-anethole, showed considerable inhibitory action of 5-LOX. In particular, the IC₅₀ of trans-anethole was 51.6 μ M. In contrast, FR and the isolated compounds did not show considerable inhibitory activity on the degranulation reaction of β-hexosaminidase release from antigen-treated RBL-2H3 cells. Against arachidonic acid-induced ear edema in mice, FR and trans-anethole showed significant inhibition by oral administration at doses of 100-400 mg/kg. In conclusion, FR and several major constituents are 5-LOX inhibitors and they may have potential for treating 5-LOX-related disorders.     

Adenosine reduces GABAergic IPSC frequency via presynaptic A1 receptors in hypothalamic paraventricular neurons projecting to rostral ventrolateral medulla

Adenosine is an inhibitory modulator of neuronal transmission, including GABAergic transmission in the hypothalamus. It is known that the local GABAergic inputs tonically inhibit the hypothalamic paraventricular neurons projecting to the rostral ventrolateral medulla (RVLM; PVN-RVLM neurons) which regulate sympathetic outflow. In this study, we examined the effects of adenosine on GABAergic synaptic transmission in the PVN-RVLM neurons using whole cell patch-clamp combined with the retrograde labeling technique. Adenosine (100 μM) reversibly decreased the frequency of miniature IPSCs (from 3.41 ± 0.75 to 2.19 ± 0.49 Hz) in a concentration-dependent manner (IC₅₀ = 1.0 μM) without affecting the amplitude and the decay time constant of miniature IPSCs. Adenosine increased the paired-pulse ratio of evoked IPSCs from 1.19 ± 0.05 to 2.28 ± 0.09 (P < 0.001). The effects of adenosine was mimicked by a selective A₁ receptor agonist (CHA, 10 μM), and blocked by a selective A₁ receptor antagonist (DPCPX, 2 μM), but not by a selective A₂ receptor antagonist (DMPX, 10 μM). In conclusion, the results showed that adenosine inhibits synaptic GABA release via presynaptic A₁ receptors in the PVN-RVLM neurons, indicating a potential of adenosine A₁ receptors in regulating sympathetic tone in normal and disease states.     

Analgesic mechanism of electroacupuncture in an arthritic pain model of rats: a neurotransmitter study

Purpose

We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats.

Materials and Methods

One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA.

Results

In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group.

Conclusion

The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.     

Long-lasting neonatal inflammation enhances pain responses to subsequent inflammation,but not peripheral nerve injury in adult rats

The early postnatal period has been suggested to be the vulnerable time for structural and functional reorganization of sensory systems, and painful stimuli at this time may alter neuronal circuits, thereby leading to changes in an individual's response to pain later in life. In the present study, we examined whether inflammatory experience in the early life can affect pain responses to subsequent noxious insults later in life. The two groups of neonatal rats, treated with an inflammatory irritant and untreated, were subjected to inflammation and peripheral nerve injury in adulthood. Neonatal inflammation was induced by injection of complete Freund's adjuvant (CFA, 25 μl) into the hindpaw or tail of newborn rat pups. Adult rats which had suffered from neonatal paw inflammation at P0 were subjected to re-injection of CFA into the paw neonatally exposed to CFA or L5 spinal nerve ligation. Paw thickness and histology of inflamed paw were examined to assess the neonatal inflammation. Adult animals whose tail had been subjected to CFA injection on P3 received tail-innervating nerve injury. The results showed that the neonatal CFA-treated rats suffered from chronic inflammation, confirmed by persistent increase of paw thickness and histological result of inflamed paw. These animals showed enhanced pain responses to re-inflammatory challenge by injection of CFA (200 μl) into the neonatally inflamed paw 8 weeks after birth compared with the neonatally untreated animals. However, neuropathic pain on the hindpaw and the tail which had been induced by peripheral nerve injury in the neonatal CFA-treated group were not different from those of the untreated group. The present data suggest that early neonatal long-lasting inflammation differentially affects pain responses later in life, depending on the types of subsequent noxious insults.