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Makdoumi, Karim
Publications (10 of 15) Show all publications
Mäkeläinen, S., Gòdia, M., Hellsand, M., Viluma, A., Hahn, D., Makdoumi, K., . . . Bergström, T. F. (2019). An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genetics, 15(3), Article ID e1007873.
Open this publication in new window or tab >>An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease
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2019 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, no 3, article id e1007873Article in journal (Refereed) Published
Abstract [en]

Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.

Place, publisher, year, edition, pages
Public Library of Science, 2019
National Category
Atom and Molecular Physics and Optics Ophthalmology
Identifiers
urn:nbn:se:oru:diva-73243 (URN)10.1371/journal.pgen.1007873 (DOI)000462994900009 ()30889179 (PubMedID)2-s2.0-85063262127 (Scopus ID)
Funder
Swedish Research Council Formas, 221-2014-1005
Note

Funding Agency:

Agria och Svenska Kennelklubben Forskningsfond  P2012-0015  N2013-0020  P2014-0018  P2015-0012

Available from: 2019-03-22 Created: 2019-03-22 Last updated: 2019-06-19Bibliographically approved
Makdoumi, K., Hedin, M. & Bäckman, A. (2019). Different photodynamic effects of blue light with and without riboflavin on methicillin-resistant Staphylococcus aureus (MRSA) and human keratinocytes in vitro. Lasers in Medical Science, 34(9), 1799-1805
Open this publication in new window or tab >>Different photodynamic effects of blue light with and without riboflavin on methicillin-resistant Staphylococcus aureus (MRSA) and human keratinocytes in vitro
2019 (English)In: Lasers in Medical Science, ISSN 0268-8921, E-ISSN 1435-604X, Vol. 34, no 9, p. 1799-1805Article in journal (Refereed) Published
Abstract [en]

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infections in humans. Photodynamic therapy using blue light (450 nm) could possibly be used to reduce MRSA on different human tissue surfaces without killing the human cells. It could be less harmful than 300–400 nm light or common disinfectants. We applied blue light ± riboflavin (RF) to MRSA and keratinocytes, in an in vitro liquid layer model, and compared the effect to elimination using common disinfection fluids. MRSA dilutions (8 × 105/mL) in wells were exposed to blue light (450 nm) ± RF at four separate doses (15, 30, 56, and 84 J/cm2). Treated samples were cultivated on blood agar plates and the colony forming units (CFU) determined. Adherent human cells were cultivated (1 × 104/mL) and treated in the same way. The cell activity was then measured by Cell Titer Blue assay after 24- and 48-h growth. The tested disinfectants were chlorhexidine and hydrogen peroxide. Blue light alone (84 J/cm2) eliminated 70% of MRSA. This dose and riboflavin eradicated 99–100% of MRSA. Keratinocytes were not affected by blue light alone at any dose. A dose of 30 J/cm2 in riboflavin solution inactivated keratinocytes completely. Disinfectants inactivated all cells. Blue light alone at 450 nm can eliminate MRSA without inactivation of human keratinocytes. Hence, a high dose of blue light could perhaps be used to treat bacterial infections without loss of human skin cells. Photodynamic therapy using riboflavin and blue light should be explored further as it may perhaps be possible to exploit in treatment of skin diseases associated with keratinocyte hyperproliferation.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Blue light, Keratinocytes, MRSA, PDT, Photodynamic therapy, Riboflavin
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-73420 (URN)10.1007/s10103-019-02774-9 (DOI)000496584100008 ()30929100 (PubMedID)2-s2.0-85064269524 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital (Sweden)  461291

Örebro University 

Available from: 2019-04-04 Created: 2019-04-04 Last updated: 2019-11-27Bibliographically approved
Makdoumi, K., Nilsson, T. K. & Crafoord, S. (2017). Levels of beta-trace protein in optic disc pit with macular detachment. Acta Ophthalmologica, 95(8), 815-819
Open this publication in new window or tab >>Levels of beta-trace protein in optic disc pit with macular detachment
2017 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 8, p. 815-819Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: To report beta-trace protein (βTP) levels in the subretinal fluid (SRF) of four patients with a macular detachment associated with optic disc pit (ODP).

METHODS: Four patients with a serous retinal detachment involving the macula was operated by pars plana vitrectomy (PPV) with C2 F6 gas tamponade and peeling of internal limiting membrane (ILM). Patients with a follow-up period exceeding one year postoperatively were included in the study. The SRF was drained using a fine cannula without laser photocoagulation, and the samples were analysed using particle-enhancing nephelometry. The levels of βTP were compared to 20 routine cerebrospinal fluid (CSF) samples.

RESULTS: In four of the five samples from SRF had relatively low βTP levels, with a mean concentration of 6.6 mg/l (range 2.0 to 23.1 mg/l) compared to 16.0 mg/l (range 6.3-26.8 mg/l) in CSF. The only SRF sample within the range corresponding to normal CSF was the first sample from patient 4, and the analysis of the renewed aspirate during the second operation was 2.8 mg/l. Postoperatively, the regression of SRF was slow, but regression of SRF in the foveal region took place in all cases; however, visual acuity (VA) was improved in only half of the patients.

CONCLUSION: The results from the analysed SRF regarding βTP concentration in these patients indicate that the SRF in ODP is not identical to CSF, as the concentrations of βTP differ.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2017
Keywords
beta trace, beta-trace protein, optic disc pit, β-trace protein
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-62465 (URN)10.1111/aos.13527 (DOI)000417645900036 ()28926186 (PubMedID)2-s2.0-85030124493 (Scopus ID)
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-08-11Bibliographically approved
Makdoumi, K., Goodrich, R. & Bäckman, A. (2017). Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin. Acta Ophthalmologica, 95(5), 498-502
Open this publication in new window or tab >>Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin
2017 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 5, p. 498-502Article in journal (Refereed) Published
Abstract [en]

Purpose: To compare elimination of methicillin-resistant Staphylococcus aureus (MRSA) by exposure of blue light alone and with riboflavin.

Methods: A reference strain of MRSA was cultured and diluted in PBS with and without riboflavin (0.01%). Fifteen microlitre was added on a microscope slide, creating a fluid layer with a thickness of around 400 microns. Both of the bacterial suspensions were exposed to blue light, and the effect between exposure with and without riboflavin was compared. Evaluation involved two different wavelengths (412 and 450 nm) of blue light with a lower (5.4 J/cm(2) ) and higher dose (approximately 28.5 J/cm(2) ). The effect of 412 nm light was also evaluated for a thicker fluid layer (1.17 mm). After exposure, colony-forming units (CFUs) were determined for each solution. All measurements were repeated eight times.

Results: The reductions in bacteria were similar for both wavelengths. With riboflavin, a statistically significant elimination was observed for both 412 and 450 nm (p < 0.001). At both dosages, the mean reduction was more pronounced with the presence of riboflavin than without it. Using the higher dose, CFU reduction was 99% and 98%, respectively, for 412 and 450 nm light. The bactericidal efficacy was high also in the deeper fluid layer (93%, higher dose).

Conclusion: Riboflavin enhanced the antibacterial effect on the exposed MRSA strain of blue light for both 412 and 450 nm blue light. This indicates that blue light could be considered for possible implementation in deep corneal infections.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell Publishing Inc., 2017
Keywords
Keratitis, riboflavin, blue light, PACK-CXL, collagen cross-linking
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-55956 (URN)10.1111/aos.13409 (DOI)000405388500027 ()28205348 (PubMedID)2-s2.0-85013230688 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital (Sweden)  OLL-294081  fOLL-393791

Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2018-09-06Bibliographically approved
Makdoumi, K. & Bäckman, A. (2016). Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria. Clinical and Experimental Ophthalmology, 44(7), 582-586
Open this publication in new window or tab >>Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria
2016 (English)In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 44, no 7, p. 582-586Article in journal (Refereed) Published
Abstract [en]

Background: To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK)-collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains.

Methods: Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4x10(5)/ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n=8). The degree of elimination in resistant and non-resistant pathogens was compared.

Results: The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin-resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P=0.030).

Conclusion: UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
bacteria, resistance, riboflavin, ultraviolet, UVA
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-53635 (URN)10.1111/ceo.12723 (DOI)000386685300009 ()26867998 (PubMedID)2-s2.0-84963632197 (Scopus ID)
Note

Funding Agency:

Örebro University Hospital (Sweden) OLL-294081  OLL-393791

Available from: 2016-11-28 Created: 2016-11-25 Last updated: 2018-07-17Bibliographically approved
Bäckman, A., Makdoumi, K., Mortensen, J. & Crafoord, S. (2014). The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light. Acta Ophthalmologica, 92(7), 656-661
Open this publication in new window or tab >>The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light
2014 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 7, p. 656-661Article in journal (Refereed) Published
Abstract [en]

Purpose: To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model.

Methods: Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007-0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60min of UVA exposure (irradiance 30 and 3mW/cm(2)). Standard settings of UVA were compared with high-power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model.

Results: Bacterial eradication (%) was increased after 60 compared with 30min of UVA exposure for concentrations of 0.03-0.07% but not for 0.09% riboflavin. There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80% to 50% (p=0.01). A correlation could be calculated for the amount of riboflavin at 60min of UVA and the ability to kill bacteria (p=0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High-power UVA method was less potent in microbial elimination, eradicating only 60% of bacteria after 6min versus 97-99% after 60min in the low-power setting, compared with respective controls (p=0.02).

Conclusions: In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross-linking settings. Further studies are needed to evaluate the clinical relevance of these findings.

Place, publisher, year, edition, pages
Hoboken, USA: John Wiley & Sons, 2014
Keywords
Bacteria, cross-linking, exposure time, riboflavin, UVA
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-39452 (URN)10.1111/aos.12301 (DOI)000344162700030 ()25493311 (PubMedID)2-s2.0-84887264034 (Scopus ID)
Note

Funding Agency:

Örebro University Hospital (Sweden) - Research Funds OLL-120691

Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-08-29Bibliographically approved
Makdoumi, K., Bäckman, A., Mortensen, J., Magnuson, A. & Crafoord, S. (2013). Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba Castellanii. Graefe's Archives for Clinical and Experimental Ophthalmology, 251(2), 509-514
Open this publication in new window or tab >>Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba Castellanii
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2013 (English)In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 251, no 2, p. 509-514Article in journal (Refereed) Published
Abstract [en]

Purpose To investigate whether ultraviolet light (UVA) at 365 nm can inhibit/eliminate Acanthamoeba growth and if riboflavin would potentiate such an association.

Method: Acanthamoeba castellanii in a fluid medium with a concentration of approximately 1.7 x 10(4) protozoa/ml were prepared with (0.01 %) and without riboflavin. Exposure of UVA (dose 5.475 J/cm(2)) took place twice, with each illumination period followed by culturing of 10 mu l in peptone yeast-extract glucose (PYG) medium for 7 days. Every suspension prepared had a non-exposed control solution. Determination of Acanthamoeba was conducted daily, by count in Burker chamber days 4 through 7 after exposure. Statistical analysis was done by repeated-measurement ANOVA and post-hoc analysis for unpaired samples.

Results: The exposure of ultraviolet light resulted in an inhibited growth of Acanthamoeba compared to the non-exposed solutions, with a statistically significant reduction over time (p = 0.0003). The addition of riboflavin did not amplify the effect, and there were no tendencies for an interaction effect between UVA and riboflavin. The antiprotozoal effect of the UVA wavelength, utilized in CXL, is solely mediated by ultraviolet light, and riboflavin does not seem to amplify the antimicrobial efficacy.

Place, publisher, year, edition, pages
New York, USA: Springer, 2013
Keywords
Acanthamoeba, Acanthamoeba castellanii, UV, UVA, Riboflavin, Keratitis, Growth inhibition
National Category
Ophthalmology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-38720 (URN)10.1007/s00417-012-2176-4 (DOI)000314683200012 ()23079692 (PubMedID)2-s2.0-84877108959 (Scopus ID)
Note

Funding agency:

Orebro University Hospital, Sweden: OLL-1578 , OLL-120691 

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2018-05-22Bibliographically approved
Hellander-Edman, A., Makdoumi, K., Mortensen, J. & Ekesten, B. (2013). Corneal cross-linking in 9 horses with ulcerative keratitis. BMC Veterinary Research, 9, 128
Open this publication in new window or tab >>Corneal cross-linking in 9 horses with ulcerative keratitis
2013 (English)In: BMC Veterinary Research, ISSN 1746-6148, E-ISSN 1746-6148, Vol. 9, p. 128-Article in journal (Refereed) Published
Abstract [en]

Background: Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting.

Results: Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4-26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis.

Conclusions: CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2013
Keywords
Equine, Horse, Keratitis, Corneal ulceration, Cross-linking, Cross linking, Collagen, CXL, UVA, Riboflavin, Stromal melting
National Category
Veterinary Science
Identifiers
urn:nbn:se:oru:diva-38721 (URN)10.1186/1746-6148-9-128 (DOI)000321338700001 ()23803176 (PubMedID)2-s2.0-84879445171 (Scopus ID)
Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2017-12-05Bibliographically approved
Makdoumi, K., Mortensen, J., Sorkhabi, O., Malmvall, B.-E. & Crafoord, S. (2012). UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study. Graefe's Archives for Clinical and Experimental Ophthalmology, 250(1), 95-102
Open this publication in new window or tab >>UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study
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2012 (English)In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 250, no 1, p. 95-102Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis.

Methods: A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643).

Results: All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant.

Conclusions: This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.

Place, publisher, year, edition, pages
New York, USA: Springer, 2012
Keywords
UV, UVA, ultraviolet, riboflavin, CXL, keratitis, pilot study
National Category
Surgery Medical and Health Sciences
Research subject
Surgery; Medicine
Identifiers
urn:nbn:se:oru:diva-20752 (URN)10.1007/s00417-011-1754-1 (DOI)000299371000012 ()21874347 (PubMedID)2-s2.0-84857359468 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital (Sweden) OLL-57221

Futurum, the Academy of Health Care, Jonkoping (Sweden)

Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2018-05-08Bibliographically approved
Makdoumi, K. (2011). Ultraviolet light A (UVA) photoactivation of riboflavin as a potential therapy for infectious keratitis. (Doctoral dissertation). Örebro: Örebro universitet
Open this publication in new window or tab >>Ultraviolet light A (UVA) photoactivation of riboflavin as a potential therapy for infectious keratitis
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2011. p. 70
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 63
National Category
Medical and Health Sciences Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-20130 (URN)978-91-7668-834-2 (ISBN)
Public defence
2011-12-16, Wilandersalen, Universitetssjukhuset, Örebro, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-10-20 Created: 2011-10-20 Last updated: 2017-10-17Bibliographically approved
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