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[Combinational Overexpression of Foxa3 and Hnf4α Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes]

Fan JY, Dama G, Liu YL, Guo WY, Lin JT

Mol Biol (Mosk), 2023;57(4):668-670.
PMID: 37528786

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

Matched MeSH terms: Penicillins/metabolism
The patient who had a picnic at a waterfall and presented with haemoptysis and renal failure

Thiruventhiran T, Tan SY

Nephrol Dial Transplant, 2000 May;15(5):727-8.
PMID: 10809822
Matched MeSH terms: Penicillins/therapeutic use
Fulltext Molecular detection and genotypic characterisation of Streptococcus pneumoniae isolated from children in Malaysia

Goh SL, Kee BP, Abdul Jabar K, Chua KH, Nathan AM, Bruyne J, et al.

Pathog Glob Health, 2020 02;114(1):46-54.
PMID: 32003298 DOI: 10.1080/20477724.2020.1719325

Streptococcus pneumoniae (S. pneumoniae) is one of the main causative agents of pneumococcal diseases. To date, more than 90 distinct serotypes have been identified. Implementation of vaccines has caused a drastic reduction in vaccine-serotype pneumococcal diseases but increase in cases due to non-vaccine serotype has been observed in Malaysia. However, further investigation on different serotype incidence in Malaysia is needed and the rate of pneumococcal vaccination for new-born babies in Malaysia remains low. The recent emergence of drug-resistant S. pneumoniae (DRSP) has also been a global concern, especially penicillin resistance. This study determined the serotypes of S. pneumoniae strains (n = 95) isolated from nasopharyngeal specimens from children admitted to UMMC from 2013 to 2015. In accordance with previous studies, PCR result showed 40% of NT isolates were successfully typed as 3 less common serotypes, namely 9N/L, 17A, and 23B. The repetitive-element PCR (REP-PCR) result revealed genetic variations among the strains whereby five major clusters were observed at the similarity of 80% by clustering analysis based on fingerprint data. Penicillin-binding proteins (pbps) of selected isolates were studied by PCR and sequencing. Three strains with ≤19-mm diameter zone for Oxacillin Disc Diffusion (ODD) test previously were recorded to have mutation on all pbp1a, pbp2b, and pbp2x with MIC of 4 µg/ml, which were penicillin-intermediate resistance according to the CLSI breakpoints.

Matched MeSH terms: Penicillins/pharmacology
Fulltext Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia

Jefferies JM, Mohd Yusof MY, Devi Sekaran S, Clarke SC

PLoS One, 2014;9(6):e97912.
PMID: 24941079 DOI: 10.1371/journal.pone.0097912

Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy.

Matched MeSH terms: Penicillins/therapeutic use
Population density and antibiotic resistant of bacteria from bivalve (Perna viridis and Anadara granosa)

Asmat Armad, Nur Diana Mehat, Usup G, Rahimi Hamid

Sains Malaysiana, 2014;43:543-550.

This study was carried out to know the bacteria population density in the blood cockle (Anadara granosa) and green lipped mussel (Perna viridis), to analyse the bacteria resistance towards antibiotics and antimicrobial activity of isolates against selected pathogen. Samples of blood cockle and green lipped mussel were obtained from five areas in Kedah and Negeri Sembilan. Bacterial population densities in mussels and cockles were 3 x 102 - 8 x 108 cFulmL and 5 x 102 - 5 x 108 cFulmL, respectively. A total of 162 isolates were obtained, of which 131 isolates were from mussels and 31 isolates were from cockles. Vibrio sp. was the most dominant genus in both types of samples. Antibiotic testing of all isolates showed most were resistant to Penicillin (10 U) and most were sensitive to Ciprofloxacin (5 Jig). Most isolates (160/162) showed resistance to at least two antibiotics and 10 isolates were resistant to more than five antibiotics. Multiple antibiotic resistance indices (MAR) were calculated based on the antibiotic resistance results. Most isolates had a MAR index value of 02 which indicated the isolates were not contaminated with antibiotic residues. The highest index value was 0 .7 . Fifteen out of 39 isolates which produced beta-lactamase enzyme were tested for antimicrobial activity against selected pathogen. Results indicated that antimicrobial activity were varies among the isolates. Isolate smii-Ip produced antimicrobial activity against six out of the nine tested pathogen and none of the isolates active against Pseudomonas mirabilis.

Matched MeSH terms: Penicillins
Prevalence of salmonella sp. In African catfish (clarias gariepinus) obtained from farms and wet markets in Kelantan, Malaysia and their antibiotic resistance

Sing CK, Md. Zahirul Islam Khan, Hassan Hj. Mohd Daud, Abd. Rahman Aziz

Sains Malaysiana, 2016;45:1597-1602.

The present study was conducted to determine the prevalence and antibiotic resistance of Salmonella sp. isolated from
African catfish (Clarias gariepinus). A total of 30 catfish were harvested from four different farms and four different
wet markets. A total of 60 samples (30 catfish skins and 30 catfish intestines) were used for Salmonella sp. isolation
(pellet-method), its biochemical and serological test. Confirmation of Salmonella sp. were determined by polyvalent
O antisera and polymerase chain reaction (PCR) using genus specific primers for invA genes (DNA amplification
showed one distinct band with molecular weight of 389 bp) and the species of isolated Salmonella sp. were identified
by serotyping. The result showed 6/30 (20%) of fish or 6/60 (10%) of organ samples were positive for Salmonella sp.
Among those positive for Salmonella sp., 4/6 were from intestine samples and 2/6 were from skin samples. No significant
difference was found in the prevalence of Salmonella sp. isolates between fish harvested from farms and wet markets
(p-value= 0.406). The Salmonella serovars identified were Salmonella corvallis (n=3), Salmonella mbandaka (n=2)
and Salmonella typhmurium (n=1). Salmonella sp. isolates were resistance to Penicillin (P 10, 100%), Clindamycin
(DA 2, 100%), Tetracycline (TE 30, 100%) and Rifampicin (RD 5, 100%) and all of the isolates were susceptible or
intermediate resistance to Ceftazidime (CAZ 30) and Trimethopin (W 5). Multiple antibiotic resistance (MAR) index of
all Salmonella sp. isolates in current study was 0.67 indicating that fish sampled in the present study was under high
risk of been exposed to the tested antibiotics.

Matched MeSH terms: Penicillins
Fulltext Prevalence and antibiotic resistance patterns of Vibrio parahaemolyticus isolated from different types of seafood in Selangor, Malaysia

Tan CW, Rukayadi Y, Hasan H, Thung TY, Lee E, Rollon WD, et al.

Saudi J Biol Sci, 2020 Jun;27(6):1602-1608.
PMID: 32489301 DOI: 10.1016/j.sjbs.2020.01.002

Vibrio parahaemolyticus is a foodborne bacterial pathogen that may cause gastroenteritis in humans through the consumption of seafood contaminated with this microorganism. The emergence of antimicrobial and multidrug-resistant bacteria is another serious public health threat worldwide. In this study, the prevalence and antibiotic susceptibility test of V. parahaemolyticus in blood clams, shrimps, surf clams, and squids were determined. The overall prevalence of V. parahaemolyticus in seafood was 85.71% (120/140), consisting of 91.43% (32/35) in blood clam, 88.57% (31/35) in shrimps, 82.86% (29/35) in surf clams, and 80% (28/35) in squids. The majority of V. parahaemolyticus isolates from the seafood samples were found to be susceptible to most antibiotics except ampicillin, cefazolin, and penicillin. The MAR indices of V. parahaemolyticus isolates ranged from 0.04 to 0.71 and about 90.83% of isolates were found resistant to more than one antibiotic. The high prevalence of V. parahaemolyticus in seafood and multidrug-resistant isolates detected in this study could pose a potential risk to human health and hence appropriate control methods should be in place to minimize the potential contamination and prevent the emergence of antibiotic resistance.

Matched MeSH terms: Penicillins
Fulltext In vitro properties of designed antimicrobial peptides that exhibit potent antipneumococcal activity and produces synergism in combination with penicillin

Le CF, Yusof MY, Hassan H, Sekaran SD

Sci Rep, 2015;5:9761.
PMID: 25985150 DOI: 10.1038/srep09761

Antimicrobial peptides (AMPs) represent a promising class of novel antimicrobial agents owing to their potent antimicrobial activity. In this study, two lead peptides from unrelated classes of AMPs were systematically hybridized into a series of five hybrid peptides (DM1-DM5) with conserved N- and C-termini. This approach allows sequence bridging of two highly dissimilar AMPs and enables sequence-activity relationship be detailed down to single amino acid level. Presence of specific amino acids and physicochemical properties were used to describe the antipneumococcal activity of these hybrids. Results obtained suggested that cell wall and/or membrane targeting could be the principal mechanism exerted by the hybrids leading to microbial cell killing. Moreover, the pneumocidal rate was greater than penicillin (PEN). Combination treatment with both DMs and PEN produced synergism. The hybrids were also broad spectrum against multiple common clinical bacteria. Sequence analysis showed that presence of specific residues has a major role in affecting the antimicrobial and cell toxicity of the hybrids than physicochemical properties. Future studies should continue to investigate the mechanisms of actions, in vivo therapeutic potential, and improve rational peptide design based on the current strategy.

Matched MeSH terms: Penicillins
Fulltext In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin

Le CF, Yusof MY, Hassan MA, Lee VS, Isa DM, Sekaran SD

Sci Rep, 2015;5:11886.
PMID: 26156658 DOI: 10.1038/srep11886

We have previously designed a series of antimicrobial peptides (AMPs) and in the current study, the in vivo therapeutic efficacy and toxicity were investigated. Among all the peptides, DM3 conferred protection to a substantial proportion of the lethally infected mice caused by a strain of penicillin-resistant Streptococcus pneumoniae. Synergism was reported and therapeutic efficacy was significantly enhanced when DM3 was formulated in combination with penicillin (PEN). No toxicity was observed in mice receiving these treatments. The in silico molecular docking study results showed that, DM3 has a strong affinity towards three protein targets; autolysin and pneumococcal surface protein A (pspA). Thus AMPs could serve as supporting therapeutics in combination with conventional antibiotics to enhance treatment outcome.

Matched MeSH terms: Penicillins
Fulltext Comparison of the management of Helicobacter pylori infection between the older and younger European populations

Jonaitis P, Nyssen OP, Saracino IM, Fiorini G, Vaira D, Pérez-Aísa Á, et al.

Sci Rep, 2023 Oct 11;13(1):17235.
PMID: 37821503 DOI: 10.1038/s41598-023-43287-4

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p

Matched MeSH terms: Penicillins/therapeutic use
Management of infective endocarditis in pregnancy

Jeyamalar R, Sivanesaratnam V

Aust N Z J Obstet Gynaecol, 1991 May;31(2):123-4.
PMID: 1930032
Matched MeSH terms: Penicillins/administration & dosage; Penicillins/therapeutic use*
Fulltext Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia

Subramaniam P, Jabar KA, Kee BP, Chong CW, Nathan AM, de Bruyne J, et al.

Indian J Med Res, 2018 Aug;148(2):225-231.
PMID: 30381546 DOI: 10.4103/ijmr.IJMR_1987_16

Background & objectives: Streptococcus pneumoniae: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia.
Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.
Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.
Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

Matched MeSH terms: Penicillins/adverse effects; Penicillins/therapeutic use
Comparison of susceptibility test methods to detect penicillin susceptibility in Streptococcus pneumoniae isolates

Mohd Nasir MD, Parasakthi N

Malays J Pathol, 2004 Jun;26(1):29-33.
PMID: 16190104

The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility.

Matched MeSH terms: Penicillins/pharmacology*
Actinomycosis of the vocal cord: a case report

Fernandez SH

Malays J Pathol, 1999 Dec;21(2):111-5.
PMID: 11068416

A 30-year-old Chinese lady was admitted for hoarseness of voice of one month's duration. Clinical examination revealed a granuloma of the left vocal cord while chest X-ray showed an opacity in the lower lobe of the right lung. The provisional clinical diagnosis was tuberculous laryngitis. A biopsy of the vocal cord lesion revealed inflamed tissue with actinomycotic colonies. Cultures and sputum smears did not reveal any tuberculous bacilli. The patient responded to a 6-week course of intravenous C-penicillin, regaining her voice on day 5 of commencement of antibiotics. A subsequent CT scan of the neck and thorax revealed multiple non-cavitating nodular lesions in both lung fields, felt to be indicative of resolving actinomycosis. She was discharged well after completion of treatment. It was felt that this is a case of primary actinomycosis of the vocal cord with probably secondary pulmonary actinomycosis.

Matched MeSH terms: Penicillins/administration & dosage; Penicillins/therapeutic use
Fulltext Frequency and molecular epidemiology of Panton-Valentine leukocidin gene in Staphylococcus aureus colonising HIV-infected patients

Mohd-Zain Z, Mohd-Nawi SFA, Adnan A, Kumar S

Malays J Pathol, 2017 Aug;39(2):115-122.
PMID: 28866692 MyJurnal

BACKGROUND: HIV-infected patients pose a high risk of contracting skin and soft tissue infections caused by Staphylococcus aureus. Those who are colonized with methicillin-resistant S. aureus (MRSA) that carry Panton-Valentine leukocidin (PVL) are predisposed to severe infections that could lead to necrotic skin infections. However the association of S. aureus specifically methicillin sensitive S. aureus carrying PVL gene in HIV patients has not been widely reported. Here, we study the prevalence and the molecular epidemiology of PVL-producing S. aureus in HIV-infected patients.
METHODS: Swabs from four body sites of 129 HIV-infected patients were cultured for S. aureus and identified by standard microbiological procedures. The isolates were subjected to antimicrobial susceptibility testing by disk diffusion against penicillin, erythromycin, clindamycin, and cotrimoxazole. PCR was used to detect the PVL gene and genetic relationship between the isolates was determined by using pulse field gel electrophoresis.
RESULTS: A total of 51 isolates of S. aureus were obtained from 40 (31%) of the patients. The majority (43.1%) of the isolates were obtained from the anterior nares. Thirteen (25.5%) of all the isolates were resistant to more than one category of antibiotics, with one isolate identified as MRSA. Thirty-eight (74.5%) isolates (including the MRSA isolate) carried PVL gene where the majority (44.7%) of these isolates were from the anterior nares. A dendogram revealed that the isolates were genetically diverse with 37 distinct pulsotypes clustered in 11 groups.
CONCLUSION: S. aureus obtained from multiple sites of the HIV patients were genetically diverse without any clonality observed.

Matched MeSH terms: Penicillins
A case of madura foot successfully treated with large doses of intravenous crystalline penicillin

Geh GS

Med J Malaya, 1969 Dec;24(2):147-50.
PMID: 4244141
Matched MeSH terms: Penicillins/therapeutic use*
Haemolytic jaundice in a drugsensitive patient in Singapore

VELLA F, Phoon WO

Med J Malaya, 1959 Jun;13:309-12.
PMID: 13841617
Matched MeSH terms: Penicillins/toxicity*
Fulltext Lemierre syndrome

Lim AL, Pua KC

Med J Malaysia, 2012 Jun;67(3):340-1.
PMID: 23082433 MyJurnal

Lemierre syndrome is an uncommon disease which commonly arise from acute bacterial oropharyngeal infection. This disease was first described in 1900 by Courmont and Cade Lemierre. It is commonly caused by Fusobacterium necrophorum. Lemierre syndrome has been reported to be serious and potentially fatal in the preantibiotic era. It is characterized by an oropharyngeal infection leading to secondary septic thrombophlebitis of the internal jugular vein with embolization to the lungs and other organs. The incidence has become relatively rare at present and is usually only diagnosed when unsuspected culture results are available. We report a case of Lemierre syndrome which was recently diagnosed in our centre.

Matched MeSH terms: Penicillins/therapeutic use*
Fulltext Actinomyces infection of the mastoid: a rare entity

Subha ST, Raman R, Cheah PL, Soo Hoo TS

Med J Malaysia, 2004 Dec;59(5):680-1.
PMID: 15889574

A rare case of mastoid infection caused by actinomyces israelii is presented. This patient underwent exploratory mastoidectomy followed by long term oral pencillin. She responded well to the treatment and has been asymptomatic on follow up to date.

Matched MeSH terms: Penicillins/therapeutic use
Fulltext A case of empyema thoracis caused by actinomycosis

Hooi LN, Na BS, Sin KS

Med J Malaysia, 1992 Dec;47(4):311-5.
PMID: 1303486

A female patient who presented with left empyema thoracis caused by Actinomyces odontolyticus is reported. She responded to treatment with penicillin and metronidazole but after 3 weeks developed leucopenia complicated by gram-negative septicaemia. Leucopenia improved rapidly on withdrawal of metronidazole. Treatment was continued with a prolonged course of penicillin and she made an uneventful recovery.

Matched MeSH terms: Penicillins/therapeutic use

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